Both animals and humans show a tendency toward eating more “comfort food” (high fat, sweet food) after acute stress. Such stress eating may be contributing to the obesity epidemic, and it is important to understand the underlying psychobiological mechanisms. Prior investigations have studied what makes individuals eat more after stress; this study investigates what might make individuals eat less. Leptin has been shown to increase following a laboratory stressor, and is known to affect eating behavior. This study examined whether leptin reactivity accounts for individual differences in stress eating. To test this, we exposed forty women to standardized acute psychological laboratory stress (Trier Social Stress Test) while blood was sampled repeatedly for measurements of plasma leptin. We then measured food intake after the stressor in 29 of these women. Increasing leptin during the stressor predicted lower intake of comfort food. These initial findings suggest that acute changes in leptin may be one of the factors modulating down the consumption of comfort food following stress.
Over 50% of adults currently use dietary supplements (DS) but manufacturers do not have to prove the safety or efficacy of a DS before it is marketed. Therefore, consumers may be exposed to inaccurate DS information, may lack confidence in choosing appropriate DS and may seek advice for usage. The objective of this study was to examine trends in usage, attitudes, and sources of information regarding DS according to geographic location, demographic group, and lifestyle choices.
Eligible individuals completed a 10-item researcher-developed survey tool to determine DS use, sources of DS information, and DS-related knowledge and attitudes over the previous year. Healthy participants (637 individuals aged 21–75 years) from two population-based cohorts that had been recruited for lipoprotein assessment studies at Tufts University in Boston, Massachusetts and University of California at Davis. Outcome measures included participants’ use, beliefs regarding essentiality of DS, confidence in choosing appropriate DS, and sources of information on DS. Univariate and multivariate logistic regression were utilized to examine differences in survey responses between groups.
Of the total population 72.7% reported taking dietary supplements in the previous year. Those living on the West Coast (80.3%) had greater use than those living on the East Coast (60.7%). Those on the East Coast were more likely to believe DS were essential to health (48.7%) and to feel confident in choosing DS that were appropriate for them (51.0%). Overall, physicians were the most frequent source of DS information for more than 50% of participants on both coasts.
Because DS usage is widespread, health care providers and nutrition educators must encourage patients to discuss their DS use and be equipped to provide information conducive to safe, efficacious consumption. Tailoring interventions for healthcare providers, media sources, industry, and the public may allow for dissemination of up-to-date information regarding DS.
Dietary supplements/utilization; Dietary supplement knowledge; Attitudes; Practices
Caloric beverages may promote weight gain by simultaneously increasing total energy intake and limiting fat oxidation. During moderate intensity exercise, caloric beverage intake depresses fat oxidation by 25% or more. This randomized crossover study describes the impact of having a caloric beverage with a typical meal on fat oxidation under resting conditions. On 2 separate days, healthy normal-weight adolescents (n = 7) and adults (n = 10) consumed the same breakfast with either orange juice or drinking water and sat at rest for 3 h after breakfast. The meal paired with orange juice was 882 kJ (210 kcal) higher than the meal paired with drinking water. Both meals contained the same amount of fat (12 g). For both age groups, both meals resulted in a net positive energy balance 150 min after breakfast. Resting fat oxidation 150 min after breakfast was significantly lower after breakfast with orange juice, however. The results suggest that, independent of a state of energy excess, when individuals have a caloric beverage instead of drinking water with a meal, they are less likely to oxidize the amount of fat consumed in the meal before their next meal.
Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b) and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum ALT and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels. Conclusion: reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD.
copper; S-adenosylhomocysteine; S-adenosylhomocysteine hydrolase; inflammation; toxic-milk mouse
Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that postoperative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress.
Hyperamylinemia is common in patients with obesity and insulin resistance, coincides with hyperinsulinemia, and results in amyloid deposition. Amylin amyloids are generally considered a pancreatic disorder in type-2 diabetes. However, elevated circulating levels of amylin may also lead to amylin accumulation and proteotoxicity in peripheral organs, including the heart.
To test whether amylin accumulates in the heart of obese and type-2 diabetic patients and to uncover the effects of amylin accumulation on cardiac morphology and function.
Methods and Results
We compared amylin deposition in failing and non-failing hearts from lean, obese, and type-2 diabetic humans using immunohistochemistry and western blots. We found significant accumulation of large amylin oligomers, fibrils and plaques in failing hearts from obese and diabetic patients, but not in normal hearts and failing hearts from lean, non-diabetic humans. Small amylin oligomers were even elevated in non-failing hearts from overweight/obese patients suggesting an early state of accumulation. Using a rat model of hyperamylinemia transgenic for human amylin, we observed that amylin oligomers attach to the sarcolemma, leading to myocyte Ca2+ dysregulation, pathological myocyte remodeling, and diastolic dysfunction, starting from pre-diabetes. In contrast, pre-diabetic rats expressing the same level of wild-type rat amylin, a non-amyloidogenic isoform, exhibited normal heart structure and function.
Hyperamylinemia promotes amylin deposition in the heart causing alterations of cardiac myocyte structure and function. We propose that detection and disruption of cardiac amylin buildup may be both a predictor of heart dysfunction and a novel therapeutic strategy in diabetic cardiomyopathy.
hyperinsulinemia/hyperamylinemia; diabetic cardiomyopathy; calcium; HIP rat; UCD-T2DM rat
In addition to acquiring a better understanding of foods that may have intrinsic health benefits, increasing our knowledge of dietary components that may adversely impact health and wellness, and the levels of consumption at which these adverse effects may occur, should also be an important priority for the Foods for Health initiative. This review discusses the evidence that additional research is needed to determine the adverse effects of consuming added sugars containing fructose. Current guidelines recommend limiting sugar consumption in order to prevent weight gain and promote nutritional adequacy. However recent data suggests that fructose consumption in humans results in increased visceral adiposity, lipid dysregulation, and decreased insulin sensitivity, all of which have been associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed model for the differential effects of fructose and glucose is presented. The only published study to directly compare the effects of fructose with those of commonly consumed dietary sweeteners, high fructose corn syrup and sucrose, indicates that high fructose corn syrup and sucrose increase postprandial triglycerides comparably to pure fructose. Dose-response studies investigating the metabolic effects of prolonged consumption of fructose by itself, and in combination with glucose, on lipid metabolism and insulin sensitivity in both normal weight and overweight/obese subjects are needed.
Fructose; glucose; visceral adiposity; insulin sensitivity; cardiovascular disease; postprandial hypertriglyceridemia; small dense low density lipoprotein
Our laboratory has investigated two hypotheses regarding the effects of fructose consumption: 1) The endocrine effects of fructose consumption favor a positive energy balance, and 2) Fructose consumption promotes the development of an atherogenic lipid profile. In previous short- and long-term studies, we demonstrated that consumption of fructose-sweetened beverages with 3 meals results in lower 24-hour plasma concentrations of glucose, insulin, and leptin in humans compared with consumption of glucose-sweetened beverages. We have also tested whether prolonged consumption of high-fructose diets could lead to increased caloric intake or decreased energy expenditure, thereby contributing to weight gain and obesity. Results from a study conducted in rhesus monkeys produced equivocal results. Carefully controlled and adequately powered long-term studies are needed to address these hypotheses. In both short- and long-term studies we demonstrated that consumption of fructose-sweetened beverages substantially increases postprandial triacylglycerol concentrations compared with glucose-sweetened beverages. In the long-term studies, apolipoproteinB concentrations were also increased in subjects consuming fructose, but not those consuming glucose. Data from a short-term study comparing consumption of beverages sweetened with fructose, glucose, high fructose corn syrup (HFCS) and sucrose, suggest that HFCS and sucrose increase postprandial triacylglycerol to an extent comparable to that induced by 100% fructose alone. Increased consumption of fructose-sweetened beverages along with increased prevalence of obesity, metabolic syndrome, and type 2 diabetes underscore the importance of investigating the metabolic consequences fructose consumption in carefully controlled experiments.
Fructose; glucose; insulin; leptin; lipids; triacylglycerol; apolipoprotein-B
HIV-infected individuals are at risk for decreased bone mineral density (BMD). The known risk factors for bone loss do not fully explain the increased risk in this population. There is emerging evidence that leptin, a hormone secreted by adipocytes, plays an important role in bone metabolism. Several studies have assessed the relationship between leptin and bone density in healthy adults, but there are few such studies in HIV-infected individuals. Furthermore, HIV infected individuals on antiretroviral therapy are at increased risk for altered fat distribution, which may impact the relationship between leptin and BMD. In a cross-sectional analysis of data in 107 HIV-infected men, we determined whether serum leptin levels were associated with whole-body BMD and bone mineral content measured by dual-energy X-ray absorptiometry (DEXA), after adjusting for confounders including body fat distribution. We found an inverse association between leptin and bone density in those with peripheral lipoatrophy, defined objectively as <3 kg appendicular fat by DEXA, but no such relationship was seen in those with >3 kg appendicular fat. This result suggests that fat distribution may modify the relationship between leptin and bone density.
The incidence of insulin resistance has increased dramatically over the past several years, and we and others have proposed that this increase may at least in part be attributable to increased dietary fructose consumption. However, a major limitation to the study of diet-induced insulin resistance is the lack of relevant animal models. Numerous studies, mostly in rodents, have demonstrated that diets high in fructose induce insulin resistance; however, important metabolic differences exist between rodents and primates. Thus, the results of metabolic studies performed in primates are substantively more translatable to human physiology, underscoring the importance of establishing nonhuman primate models of common metabolic conditions. In this report, we demonstrate that a high-fructose diet in rhesus monkeys produces insulin resistance and many features of the metabolic syndrome, including central obesity, dyslipidemia, and inflammation within a short period of time; moreover, a subset of monkeys developed type 2 diabetes. Given the rapidity with which the metabolic changes occur, and the ability to control for many factors that cannot be controlled for in humans, fructose feeding in rhesus monkeys represents a practical and efficient model system in which to investigate the pathogenesis, prevention, and treatment of diet-induced insulin resistance and its related co-morbidities.
The results of short-term studies in humans suggest that, compared with glucose, acute consumption of fructose leads to increased postprandial energy expenditure and carbohydrate oxidation and decreased postprandial fat oxidation. The objective of this study was to determine the potential effects of increased fructose consumption compared to isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions.
As part of a parallel arm study, overweight/obese male and female subjects, 40–72 y, consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention.
Consumption of fructose, but not glucose, led to significant decreases of net postprandial fat oxidation and significant increases of net postprandial carbohydrate oxidation (P < 0.0001 for both). Resting energy expenditure decreased significantly from baseline values in subjects consuming fructose (P = 0.031) but not in those consuming glucose.
Increased consumption of fructose for 10 weeks leads to marked changes of postprandial substrate utilization including a significant reduction of net fat oxidation. In addition, we report that resting energy expenditure is reduced compared to baseline values in subjects consuming fructose-sweetened beverages for 10 weeks.
fructose; fat oxidation; carbohydrate oxidation; energy expenditure; metabolic rate; humans
Since Zilversmit first proposed postprandial lipemia as the most common risk of cardiovascular disease, chylomicrons (CM) and CM remnants have been thought to be the major lipoproteins which are increased in the postprandial hyperlipidemia. However, it has been shown over the last two decades that the major increase in the postprandial lipoproteins after food intake occurs in the very low density lipoprotein (VLDL) remnants (apoB100 particles), not CM or CM remnants (apoB48 particles). This finding was obtained using the following three analytical methods; isolation of remnant-like lipoprotein particles (RLP) with specific antibodies, separation and detection of lipoprotein subclasses by gel permeation HPLC and determination of apoB48 in fractionated lipoproteins by a specific ELISA. The amount of the apoB48 particles in the postprandial RLP is significantly less than the apoB100 particles, and the particle sizes of apoB48 and apoB100 in RLP are very similar when analyzed by HPLC. Moreover, CM or CM remnants having a large amount of TG were not found in the postprandial RLP. Therefore, the major portion of the TG which is increased in the postprandial state is composed of VLDL remnants, which have been recognized as a significant risk for cardiovascular disease.
Postprandial remnant lipoproteins; Chylomicron remnants; Very low density lipoprotein (VLDL) remnants; apoB-48; apoB-100; Remnant-like lipoprotein particles (RLP); RLP-triglyceride (RLP-TG); RLP-cholesterol (RLP-C)
Psychological distress and metabolic dysregulation are associated with markers of accelerated cellular aging, including reduced telomerase activity and shortened telomere length. We examined whether participation in a mindfulness-based intervention, and, secondarily, improvements in psychological distress, eating behavior, and metabolic factors are associated with increases in telomerase activity in peripheral blood mononuclear cells (PBMCs).
We enrolled 47 overweight/obese women in a randomized waitlist-controlled pilot trial (n = 47) of a mindfulness-based intervention for stress eating and examined changes in telomerase activity from pre- to post-intervention. In secondary analyses, changes in telomerase activity across the sample were examined in relation to pre- to post-intervention changes in psychological distress, eating behavior, and metabolic factors (weight, serum cortisol, fasting glucose and insulin, and insulin resistance).
Both groups increased in mean telomerase activity over 4 months in intent-to-treat and treatment efficacy analyses (p < 0.001). Nonsignificant trends showed that greater attendance was associated with increases in telomerase, and telomerase increases were 18% higher among ‘as treated’ participants compared to controls. Across groups, changes in chronic stress, anxiety, dietary restraint, dietary fat intake, cortisol, and glucose were negatively correlated with changes in telomerase activity. In exploratory analyses, decreases in dietary fat intake partially mediated the association between dietary restraint and telomerase activity with marginal significance.
While there was no clear effect of the intervention on telomerase activity, there was a striking pattern of correlations between improvements in psychological distress, eating behavior, and metabolic health and increases in telomerase activity. These findings suggest that telomerase activity may be in part regulated by levels of both psychological and metabolic stress.
Stress; Anxiety; Mindfulness; Dietary restraint; Telomerase; Cell aging; Cortisol
Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes.
This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans.
Galectin-12, a member of the galectin family of animal lectins, is preferentially expressed in adipocytes. We recently reported that this galectin is localized on lipid droplets, specialized organelles for fat storage. Galectin-12 regulates lipid degradation (lipolysis) by modulating lipolytic protein kinase A (PKA) signaling. Mice deficient in galectin-12 exhibit enhanced adipocyte lipolysis, increased mitochondria respiration, reduced adiposity and ameliorated insulin resistance associated with weight gain. The results suggest that galectin-12 may be a useful target for treatment of obesity-related metabolic conditions, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Most previously described galectins largely reside in the cytosol, although they can also be induced to become associated with membrane-containing structures. Along with an in-depth characterization of galectin-12, this mini-review comments on this first report of a galectin normally localized specifically in an organelle that performs an important intracellular function. Further studies will help shed light on how this protein regulates cellular homeostasis, especially energy homeostasis, and provide additional insight into the intracellular functions of galectins.
adipocyte; adipose tissue; galectin; galectin-12; insulin sensitivity; lipid metabolism; lipolysis
N-3 fatty acids are associated with favorable, and obesity with unfavorable, concentrations of chronic disease risk biomarkers.
We examined whether high eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intakes, measured as percentages of total red blood cell (RBC) fatty acids, modify associations of obesity with chronic disease risk biomarkers.
In a cross-sectional study of 330 Yup'ik Eskimos, generalized additive models (GAM) and linear and quadratic regression models were used to examine associations of BMI with biomarkers across RBC EPA and DHA categories.
Median (5th–95th percentile) RBC EPA and DHA were 2.6% (0.5–5.9%) and 7.3% (3.3–8.9%), respectively. In regression models, associations of BMI with triglycerides, glucose, insulin, C-reactive protein (CRP) and leptin differed significantly by RBC EPA and DHA. The GAM confirmed regression results for triglycerides and CRP: At low RBC EPA and RBC DHA, the predicted increases in triglycerides and CRP concentrations associated with a BMI increase from 25 to 35 were 99.5±45.3 mg/dl (106%) and 137.8±71.0 mg/dl (156%), respectively, for triglycerides and 1.2±0.7 mg/l (61%) and 0.8±1.0 mg/l (35%), respectively, for CRP. At high RBC EPA and RBC DHA, these predicted increases were 13.9±8.1 mg/dl (23%) and 12.0±12.3 mg/dl (18%), respectively, for triglycerides and 0.5±0.5 mg/l (50%) and −0.5±0.6 mg/l (−34%), respectively, for CRP.
In this population, high RBC EPA and DHA were associated with attenuated dyslipidemia and low-grade systemic inflammation among overweight and obese persons. This may help inform recommendations for n-3 fatty acid intakes in the reduction of obesity-related disease risk.
EPA; DHA; generalized additive models; Yup'ik Eskimos; triglycerides; C-reactive protein
The efficacy of liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, to prevent or delay diabetes in UCD-T2DM rats, a model of polygenic obese type 2 diabetes, was investigated.
RESEARCH DESIGN AND METHODS
At 2 months of age, male rats were divided into three groups: control, food-restricted, and liraglutide. Animals received liraglutide (0.2 mg/kg s.c.) or vehicle injections twice daily. Restricted rats were food restricted to equalize body weights to liraglutide-treated rats. Half of the animals were followed until diabetes onset, whereas the other half of the animals were killed at 6.5 months of age for tissue collection.
Before diabetes onset energy intake, body weight, adiposity, and liver triglyceride content were higher in control animals compared with restricted and liraglutide-treated rats. Energy-restricted animals had lower food intake than liraglutide-treated animals to maintain the same body weights, suggesting that liraglutide increases energy expenditure. Liraglutide treatment delayed diabetes onset by 4.1 ± 0.8 months compared with control (P < 0.0001) and by 1.3 ± 0.8 months compared with restricted animals (P < 0.05). Up to 6 months of age, energy restriction and liraglutide treatment lowered fasting plasma glucose and A1C concentrations compared with control animals. In contrast, liraglutide-treated animals exhibited lower fasting plasma insulin, glucagon, and triglycerides compared with both control and restricted animals. Furthermore, energy-restricted and liraglutide-treated animals exhibited more normal islet morphology.
Liraglutide treatment delays the development of diabetes in UCD-T2DM rats by reducing energy intake and body weight, and by improving insulin sensitivity, improving lipid profiles, and maintaining islet morphology.
Background & Aims
Bariatric surgery has been shown to reverse type 2 diabetes, however the mechanisms by which this occurs remain undefined. Ileal interposition (IT) is a surgical model that isolates the effects of increasing the delivery of unabsorbed nutrients to the lower gastrointestinal tract. In this study we investigated the effects of IT surgery on glucose tolerance and diabetes onset in UCD-T2DM rats, a polygenic obese animal model of type 2 diabetes.
IT or sham surgery was performed on 4 month old male UCD-T2DM rats. All animals underwent an oral glucose tolerance test (OGTT). A subset was euthanized 2 months after surgery for tissue analyses. The remainder was followed until diabetes onset and underwent an oral fat tolerance test (OFTT).
IT surgery delayed diabetes onset by 120 ± 49 days compared with sham surgery (P< 0.05) without a difference in body weight. During OGTT, IT-operated animals exhibited lower plasma glucose excursions (P< 0.05), improved early insulin secretion (P< 0.01) and 3-fold larger plasma GLP-17–36 excursions (P< 0.001) and no difference in GIP responses compared with sham-operated animals. Total plasma PYY excursions during the OFTT were 3-fold larger in IT-operated animals (P< 0.01). IT-operated animals exhibited lower adiposity (P< 0.05), smaller adipocyte size (P< 0.05), 25% less ectopic lipid deposition, lower circulating lipids and greater pancreatic insulin content compared with sham-operated animals (P< 0.05).
IT surgery delays the onset of diabetes in UCD-T2DM rats which may be related to increased nutrient-stimulated secretion of GLP-17–36 and PYY and improvements of insulin sensitivity, β-cell function and lipid metabolism.
Bariatric surgery; diabetes prevention; glucagon-like peptide-1; peptide-YY
Two recent publications report that non-fasting triglycerides concentrations in plasma are more predictive of cardiovascular events than conventional measurements of fasting triglycerides. While these observations are consistent with the previous studies, direct correlations between remnant lipoprotein triglyceride (RLP-TG) and remnant lipoprotein cholesterol (RLP-C), which are also considered to be risk factors for cardiovascular disease, and fasting and postprandial TG have not been investigated.
On four different days, both fasting and postprandial blood samples were collected from twenty-three overweight to obese men and women at UC Davis and analyzed for plasma concentrations of TG, RLP-C and RLP-TG.
Significantly higher correlations between plasma TG and RLPs were observed in the postprandial state (RLP-C r2=0.85; RLP-TG r2=0.92) than in the fasting state (RLP-C r2=0.61; RLP-TG r2=0.73). The differences in the correlations between the fasting and postprandial TG and RLPs were statistically significant (p<0.001). The increase of RLP-TG (postprandial RLP-TG minus fasting RLP-TG) consisted of approximately 80% of the total increase of TG (postprandial TG minus fasting TG).
Postprandial TG versus remnant lipoprotein concentrations were significantly more correlated when compared with fasting TG vs RLP concentrations. The increased TG in the postprandial state was mainly consisted of TG in remnant lipoproteins. Therefore, the increased sensitivity of non-fasting TG in predicting the risk for cardiovascular events may be directly explained by the increase of remnant lipoproteins in the postprandial state.
Triglycerides; Remnant lipoproteins (RLP); RLP-Cholesterol (C); RLP-Triglyceride (TG); Cardiovascular Events; Fasting and Postprandial State
Fructose consumption in the USA has increased over the past three decades. During this time, obesity, insulin resistance and the metabolic syndrome have also increased in prevalence. While diets high in fructose have been shown to promote insulin resistance and increase TAG concentrations in animals, there are insufficient data available regarding the long-term metabolic effects of fructose consumption in humans. The objective of the present study was to investigate the metabolic effects of 10-week consumption of fructose-sweetened beverages in human subjects under energy-balanced conditions in a controlled research setting. Following a 4-week weight-maintaining complex carbohydrate diet, seven overweight or obese (BMI 26.8–33.3 kg/m2) postmenopausal women were fed an isoenergetic intervention diet, which included a fructose-sweetened beverage with each meal, for 10 weeks. The intervention diet provided 15% of energy from protein, 30% from fat and 55% from carbohydrate (30% complex carbohydrate, 25% fructose). Fasting and postprandial glucose, insulin, TAG and apoB concentrations were measured. Fructose consumption increased fasting glucose concentrations and decreased meal-associated glucose and insulin responses (P=0.0002, P=0.007 and P=0.013, respectively). Moreover, after 10 weeks of fructose consumption, 14 h postprandial TAG profiles were significantly increased, with the area under the curve at 10 weeks being 141% higher than at baseline (P=0.04). Fructose also increased fasting apoB concentrations by 19% (P=0.043 v. baseline). In summary, consumption of fructose-sweetened beverages increased postprandial TAG and fasting apoB concentrations, and the present results suggest that long-term consumption of diets high in fructose could lead to an increased risk of CVD.
Fructose; Glucose; Insulin; Hypertriacylglycerolaemia; Apolipoprotein-B
We have reported that compared with glucose-sweetened beverages, consuming fructose-sweetened beverages with meals results in lower 24-h circulating glucose, insulin and leptin concentrations, and elevated triacylglycerol (TG). However, pure fructose and glucose are not commonly used as sweeteners. High fructose corn syrup (HFCS) has replaced sucrose as the predominant sweetener in beverages in the U.S.
We compared the metabolic/endocrine effects of HFCS with sucrose, and in a subset of subjects with pure fructose and glucose.
34 men and women consumed 3 isocaloric meals with either sucrose- or HFCS-sweetened beverages, and blood samples were collected over 24 hours. Eight of the male subjects were also studied when fructose- or glucose-sweetened beverages were consumed.
In 34 subjects, 24-h glucose, insulin, leptin, ghrelin and TG profiles were similar between days that sucrose or HFCS were consumed. Postprandial TG excursions after HFCS or sucrose were larger in men than women. In the men in whom the effects of 4 sweeteners were compared, the 24-h glucose and insulin responses induced by HFCS and sucrose were intermediate between the lower responses during consumption of fructose and the higher responses during glucose. Unexpectedly, postprandial TG profiles after HFCS or sucrose were not intermediate, but comparably high as after pure fructose.
Sucrose and HFCS do not have substantially different short-term endocrine/metabolic effects. In male subjects, short-term consumption of sucrose and HFCS resulted in postprandial TG responses comparable to those induced by fructose.
glucose; fructose; high fructose corn syrup; sucrose; insulin; leptin; ghrelin; triacylglycerol; free fatty acids; postprandial hypertriacylglycerolemia; humans
Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic β-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 18–30 y, mean BMI=21.7±1.6 kg/m2) were infused for 48-h with either saline (50 ml/h) or 15% glucose (200 mg/m2/min). Subjects ingested a 600 kcal mixed nutrient meal 3-h after infusion termination. Blood samples were taken during the 48-h and for 4 hours following food ingestion. The 48-h glucose infusion elicited a metabolic profile of a glucose intolerant obese subjects, with increased plasma glucose, insulin and leptin (all P<0.01) and increased HOMA-IR (P<0.001). During meal ingestion, early insulin secretion was increased (P<0.05) but postprandial glucose (P<0.01) and insulin (P<0.01) excursions were lower following the glucose infusion. Postprandial plasma triglyceride concentrations were increased after glucose compared with saline. Food intake and hunger ratings were not different between the two conditions. Plasma leptin levels were inversely correlated with hunger (P<0.03) in both conditions and with food intake (P<0.003) during the glucose condition only. Thus, a 48-h glucose infusion does not impair postprandial hormonal responses, alter food intake or hunger in normal weight subjects. The glucose-induced increases in plasma leptin result in a stronger inverse relationship between plasma leptin and hunger as well as food intake. These data are the first to demonstrate a relationship between leptin and hunger in normal weight, non-calorically restricted human subjects.
leptin; insulin; food intake; insulin sensitivity; triglycerides
Adiponectin, a protein, secreted by adipose tissue has anti-atherogenic, anti-inflammatory, and insulin-sensitizing actions. We examined the relationship between plasma adiponectin and adiposity, insulin resistance, plasma lipids, glucose, leptin and anthropometric measurements in adult 316 men and 353 women Yup’ik Eskimos in Southwest Alaska. Adiponectin concentration was negatively associated with BMI, percent of body fat, sum of skin folds, waist circumference, triglycerides, insulin resistance (HOMA-IR), fasting insulin, and leptin in both men and women, and also with glucose in women. Adiponectin concentration correlated positively with high density lipoprotein cholesterol (HDL-C) concentration, and also with low density lipoprotein cholesterol in women. Insulin sensitive individuals (HOMA-IR < 3.52, n = 442) had higher plasma adiponectin concentrations than more insulin resistant individuals (HOMA-IR ≥ 3.52, n = 224): 11.02 ± 0.27 μg/mL vs. 8.26 ± 0.32 μg/mL, P <.001. Adiponectin concentrations did not differ between groups of participants with low and high level of risk for developing coronary heart disease. No difference in plasma adiponectin levels was found among Yup’ik Eskimos and Caucasians matched for sex, age and BMI. In conclusion, circulating adiponectin concentrations were most strongly associated with sum of skin folds in Yup’ik men and with HDL-C levels, sum of skin folds, waist circumference, insulin and triglycerides concentrations in Yup’ik women.
coronary heart disease; central adiposity; glucose; HOMA-IR; type 2 diabetes
Despite the widely reported inverse associations with insulin resistance and adiposity, adiponectin has been associated with both increased and decreased risk of cardiovascular disease. We examined whether adiponectin is associated with total and cardiovascular mortality in a large population of older adults.
We analyzed data from 3,075 well-functioning adults ages 69–79 years. Total adiponectin concentrations were measured at baseline and body composition was measured with abdominal and thigh CT scans. Mortality data was obtained over 6.6±1.6 years. We used Cox proportional hazards models adjusting for covariates in stages to examine the association between adiponectin and total and cardiovascular mortality.
There were 679 deaths and 38% were from cardiovascular disease. Unadjusted levels of adiponectin were not associated with total or cardiovascular mortality. However, after adjusting for sex and race, adiponectin was associated with an increased risk of both total (HR 1.26, 95% CI 1.15–1.37, per SD) and cardiovascular mortality (HR 1.35, 95% CI 1.17–1.56, per SD). Further adjustment for study site, smoking, hypertension, diabetes, prevalent heart disease, HDL, LDL, cystatin C, fasting insulin, triglycerides, BMI, visceral fat, thigh intermuscular fat, and thigh muscle area did not attenuate this association. This association between adiponectin and increased mortality risk did not vary by sex, race, BMI, diabetes, smoking, or weight loss.
Higher levels of adiponectin were associated with increased risk of total and cardiovascular mortality in this study of well-functioning community-dwelling older persons. This paradoxical association needs further study of underlying factors that might explain these results including differential association for high molecular weight adiponectin.
The metabolic syndrome (MetS) confers an increased risk for diabetes and cardiovascular disease. Although high-sensitive C-reactive protein (hsCRP) concentrations are higher and adiponectin concentrations lower in MetS, there is no reliable biochemical measure that can capture its various features. We evaluated whether hsCRP, adiponectin, or the ratio of adiponectin or its oligomers, especially the high-molecular-weight (HMW) oligomer, to hsCRP predict MetS in 123 subjects with MetS compared with that in 91 healthy control subjects. MetS subjects had significantly higher hsCRP levels and lower total adiponectin and oligomer levels relative to control subjects (P < .0001). The HMW/total adiponectin and adiponectin/CRP ratios were significantly lower in MetS subjects than control subjects (P < .005). The odds ratio (OR) of MetS using the 75th percentile cutoff for CRP was 3.8 (95% confidence interval [CI], 2.1–6.8) and equivalent to low total adiponectin (OR, 2.5; 95% CI, 1.3–4.5), its oligomers, or the adiponectin/hsCRP ratio (OR, 2.6; 95% CI, 1.5, 4.8). Thus, measurements of CRP, adiponectin, or its oligomers provide robust biomarkers for predicting MetS.
C-reactive protein; Adiponectin; Biomarker; Metabolic syndrome