As a result of the rising epidemic of obesity, understanding body fat distribution and its clinical implications is critical to timely treatment. Visceral adipose tissue is a hormonally active component of total body fat, which possesses unique biochemical characteristics that influence several normal and pathological processes in the human body. Abnormally high deposition of visceral adipose tissue is known as visceral obesity. This body composition phenotype is associated with medical disorders such as metabolic syndrome, cardiovascular disease and several malignancies including prostate, breast and colorectal cancers. Quantitative assessment of visceral obesity is important for evaluating the potential risk of development of these pathologies, as well as providing an accurate prognosis. This review aims to compare different methods of measuring visceral adiposity with emphasis on their advantages and drawbacks in clinical practice.
Body fat deposition and excess free fatty acid (FFA) metabolism contribute to dyslipidemia and the adverse health consequences of obesity. Individuals with upper body obesity have impaired functioning of adipocytes, the primary fatty acid storage site. Excess visceral fat is strongly associated with impaired suppression of FFA release in response to insulin, as well as with hypertriglyceridemia and low concentrations of high density lipoprotein (HDL) cholesterol. High FFA concentrations can induce insulin resistance in muscle and liver. Furthermore, failure of hyperinsulinemia to normally suppress FFA is associated with impaired carbohydrate oxidation and muscle glucose storage, reduced hepatic insulin clearance and elevated triglycerides. Understanding the impact of body fat distribution on FFA metabolism and dyslipidemia is critical for determining the link between overweight and obesity and cardiovascular disease risk. In the current review, we will explore the relationship between adipose tissue, body fat depots, and FFA metabolism.
free fatty acid; fat depots; dyslipidemia
Although obesity is a major background of life style-related diseases such as diabetes mellitus, lipid disorder, hypertension and cardiovascular disease, the extent of whole body fat accumulation does not necessarily the determinant for the occurrence of these diseases. We developed the method for body fat analysis using CT scan and established the concept of visceral fat obesity, in other word metabolic syndrome in which intra-abdominal visceral fat accumulation has an important role in the development of diabetes, lipid disorder, hypertension and atherosclerosis. In order to clarify the mechanism that visceral fat accumulation causes metabolic and cardiovascular diseases, we have analyzed gene expression profile in subcutaneous adipose tissue and visceral adipose tissue. From the analysis, we found that adipose tissue, especially visceral adipose tissue expressed abundantly the genes encoding bioactive substances such as cytokines, growth factors and complements. In addition to known bioactive substances, we found a novel collagen-like protein which we named adiponectin. Adiponectin is present in plasma at a very high concentration and is inversely associated with visceral fat accumulation. Adiponectin has anti-diabetic, anti-hypertensive and anti-atherogenic properties and recent studies revealed that this protein has an anti-inflammatory and anti-oncogenic function. Therefore hypoadiponectinemia induced by visceral fat accumulation should become a strong risk factor for metabolic and cardiovascular diseases and also some kinds of cancers.
In this review article, I would like to discuss the mechanism of life style-related diseases by focusing on the dysregulation of adiponectin related to obesity, especially visceral obesity.
visceral fat; metabolic syndrome; adiponectin; hypoadiponectinemia
Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate that adipocyte precursor cells (APCs) isolated from visceral and subcutaneous white adipose depots of mice have distinct patterns of gene expression, differentiation potential, and response to environmental and genetic influences. APCs derived from subcutaneous fat differentiate well in the presence of classical induction cocktail, whereas those from visceral fat differentiate poorly but can be induced to differentiate by addition of bone morphogenetic protein (BMP)-2 or BMP-4. This difference correlates with major differences in gene expression signature between subcutaneous and visceral APCs. The number of APCs is higher in obesity-prone C57BL/6 mice than obesity-resistant 129 mice, and the number in both depots is increased by up to 270% by exposure of mice to high-fat diet. Thus, APCs from visceral and subcutaneous depots are dynamic populations, which have intrinsic differences in gene expression, differentiation properties, and responses to environmental/genetic factors. Regulation of these populations may provide a new target for the treatment and prevention of obesity and its metabolic complications.
A great amount of literature has demonstrated a connection between obesity, visceral fat and the metabolic disorders such as hyperglycemia, hypertension, and hyperlipidemia. Lately, there has been an increased interest in understanding if cancer is related to obesity and visceral fat accumulation. The prevalence of both obesity and cancer are increasing and there has been keen interest in the relationship between visceral adiposity and the biology of cancers. White adipose tissue (WAT) provides a limitless capacity for triglyceride storage vital for survival. The concurrent rise in insulin, glucose, and lipids during meals stimulates triglyceride formation and storage in WAT. WAT is also recognized as an endocrine organ that secretes multiple cytokines such as leptin and adiponectin. In addition, leptin and adiponectin have been adipocytokines that attracted attention for cancer research. Thus, in this review, we will describe recent progress made in obesity, visceral adiposity, leptin and adiponectin in the involvement of various cancers.
obesity; visceral adiposity; leptin; adiponectin; cancer
Excess visceral adiposity induces chronic subclinical inflammation resulting in the metabolic syndrome. Whether excess visceral adiposity impacts posttraumatic inflammatory profiles more is unknown. We hypothesized that obese patients (body mass index >30 kg/m2) with higher visceral to subcutaneous adipose tissue distribution would have increased inflammatory outcomes.
A secondary analysis of a prospective cohort of adult trauma patients requiring >48 hours of intensive care unit care over a 55-month period was analyzed. Body fat distribution was determined by radiologist review of computed tomography scans at L1. Concentric freeform regions were defined manually, and area was calculated. Visceral adiposity was defined as subcutaneous fat area: visceral area >1.35 (the median), whereas subcutaneous adiposity was defined as a ratio <1.35. Primary outcomes were proinflammatory biomarkers known to be associated with chronic visceral obesity (white blood cell count, interleukin 1, 2, 4, 6, 8, 10, and tumor necrosis factor α). Secondary outcomes were all-cause in-hospital mortality, adult respiratory distress syndrome, and nosocomial infections.
Two hundred eighty-one (19%) obese patients with available computed tomography scans from 1,510 trauma patients were included. Visceral adiposity included 140 patients, subcutaneous adiposity included 141 patients. The two groups were similar in regards to age, Trauma Injury Severity Score, and Acute Physiology and Chronic Health Evaluation II score. There was no difference (p > 0.05) in proinflammatory biomarkers. Patients with visceral adiposity had similar clinical outcomes including mortality (p = 0.56), adult respiratory distress syndrome (p = 0.69), and infection (0.43).
Visceral body fat distribution in obese patients is not associated with increased inflammatory profiles or clinical outcomes after trauma. The impact of injury severity on acute inflammation likely overwhelms the metabolic disturbances and subclinical inflammation associated with visceral obesity in the chronic setting.
Obesity; Trauma; Visceral adiposity; Visceral obesity
Neuropeptide Y (NPY) is induced in peripheral tissues such as adipose tissue with obesity. The mechanism and function of NPY induction in fat are unclear. Given the evidence that NPY can modulate inflammation, we examined the hypothesis that NPY regulates the function of adipose tissue macrophages (ATMs) in response to dietary obesity in mice. NPY was induced by dietary obesity in the stromal vascular cells of visceral fat depots from mice. Surprisingly, the induction of Npy was limited to purified ATMs from obese mice. Significant basal production of NPY was observed in cultured bone marrow derived macrophage and dendritic cells (DCs) and was increased with LPS stimulation. In vitro, addition of NPY to myeloid cells had minimal effects on their activation profiles. NPY receptor inhibition promoted DC maturation and the production of IL-6 and TNFα suggesting an anti-inflammatory function for NPY signaling in DCs. Consistent with this, NPY injection into lean mice decreased the quantity of M1-like CD11c+ ATMs and suppressed Ly6chi monocytes. BM chimeras generated from Npy−/− donors demonstrated that hematopoietic NPY contributes to the obesity-induced induction of Npy in fat. In addition, loss of Npy expression from hematopoietic cells led to an increase in CD11c+ ATMs in visceral fat with high fat diet feeding. Overall, our studies suggest that NPY is produced by a range of myeloid cells and that obesity activates the production of NPY in adipose tissue macrophages with autocrine and paracrine effects.
To determine the relative contribution of obesity and visceral white adipose tissue (WAT) to metabolic syndrome, we developed a model that is susceptible to high-fat diet-induced obesity and insulin resistance using male KK/Ta mice. The ratio of WAT weight to body weight was greater in the high-fat diet group compared with the control group in 10-, 14-, and 22-week-old mice. The increase in visceral WAT preceded development of fatty liver and insulin resistance. Adiponectin mRNA expression in WAT was markedly decreased before the decrease in its plasma levels or the development of insulin resistance. Insulin resistance appeared in association with fatty infiltration and TNF-α expression in the liver in 22-week-old mice. These data indicate that our mouse model would be useful for future studies that investigate the role of visceral WAT and its products in the development of metabolic syndrome.
metabolic syndrome; high-fat diet; white adipose tissue; fatty liver
Accumulating evidence suggests a cross-sectional association between oxidative stress and type 2 diabetes (T2D). Systemic oxidative stress, as measured by oxidized LDL (oxLDL), has been correlated with visceral fat. We examined the relationship between oxLDL, and T2D- and obesity-related traits in a bi-racial sample of 2,985 subjects at baseline and after 7 years of follow-up.
We examined six T2D-related traits (T2D status, HbA1c, fasting glucose, insulin, adiponectin and HOMA-IR) as well as six obesity-related traits (obesity status, BMI, leptin, % body fat, visceral and subcutaneous fat mass) using logistic and linear regression models.
In all subjects at baseline, oxLDL was positively associated with T2D (OR=1.3,95% CI:1.1–1.5), fasting glucose (β=0.03±0.006), HbA1c (β=0.02±0.004), fasting insulin (β=0.12±0.02), HOMA-IR (β=0.13±0.02) and negatively with adiponectin (β=−0.16±0.03), (all p<0.001). The strength and magnitude of these associations did not differ much between blacks and whites. In both blacks and whites, oxLDL was also associated with obesity (OR=1.3, 95% CI:1.1–1.4) and 3 of its related traits (β=0.60±0.14 for BMI, β=0.74±0.17 for % body fat, β=0.29±0.06 for visceral fat;
all p<0.001). Furthermore, of 4 traits measured after 7 years of follow-up (fasting glucose, HbA1c, BMI and % fat), their relationship with oxLDL were similar to baseline observations. No significant association was found between oxLDL and incident T2D. Interestingly, oxLDL was significantly associated with % change in T2D- and obesity-related traits in whites but not in blacks.
Our data suggest that systemic oxidative stress may be a novel risk factor for T2D and obesity.
oxLDL; diabetes; oxidation; obesity
Purpose of review
Despite a strong correlation between obesity and insulin resistance, 25% of severely obese (BMI >40) individuals are insulin sensitive. In this review, we will examine the factors in adipose tissue that distinguish the two groups, as well as reasons for believing the insulin-sensitive group will be less disease prone.
Obesity has been linked to the metabolic syndrome with an increase in visceral (intra-abdominal) compared to subcutaneous fat. Recent studies in which adipose tissue of insulin-sensitive and insulin-resistant patients with severe obesity were compared indicate that the insulin-resistant group is also distinguished by increases in oxidative stress and decreases in AMP-activated protein kinase (AMPK) activity. In contrast, changes in the expression of genes for SIRT1, inflammatory cytokines, mitochondrial biogenesis and function, and the two α-isoforms of AMPK showed more depot variation. Studies of how these and other changes in adipose tissue respond to bariatric surgery are still in their infancy.
Available data suggest that increases in oxidative stress, decreases in AMPK activity and SIRT1 gene expression, depot-specific changes in inflammatory, mitochondrial and other genes distinguish adipose tissue of insulin resistant from insulin-sensitive individuals with severe obesity.
AMP-activated protein kinase; inflammation; insulin resistance; oxidative stress; SIRT1
The excessive accumulation of body fat is a major risk factor to develop a variety of metabolic diseases. To investigate the systematic association between the differences in gene expression profiling and adipose deposition, we used pig as a model, and measured the gene expression profiling of six variant adipose tissues in male and females from three pig breeds which display distinct fat level.
We identified various differential expressed genes among breeds, tissues and between sexes, and further used a clustering method to identify sets of functionally co-expression genes linked to different obesity-related phenotypes. Our results reveal that the subcutaneous adipose tissues mainly modulate metabolic indicators, nonetheless, the visceral adipose tissues as well as the intermuscular adipose tissue were mainly associated with the impaired inflammatory and immune response.
The present study provided the evidence of gene expression profiling that the subcutaneous adipose tissues are mainly affected the metabolism process, whereas the visceral and intermuscular adipose tissues should been term as the metabolic risk factors of obesity.
Gene expression profiling; Subcutaneous adipose tissues; Visceral adipose tissues; Pig
Past civilisations saw excess body fat as a symbol of wealth and prosperity as the general population struggled with food shortages and famine. Nowadays it is recognised that obesity is associated with co-morbidities such as cardiovascular disease and diabetes. Our views on the roll of adipose tissue have also changed, from being solely a passive energy store, to an important endocrine organ that modulates metabolism, immunity and satiety. The relationship between increased visceral adiposity and obesity-related co-morbidities has lead to the recognition that variation in fat distribution contributes to ethnic differences in the prevalence of obesity-related diseases. Our current negative view of adipose tissue may change with the use of pluripotent adipose-derived stromal cells, which may lead to future autologous stem cell therapies for bone, muscle, cardiac and cartilage disorders. Here, we briefly review the concepts that adipose tissue is an endocrine organ, that differences in body fat distribution underline the aetiology of obesity-related co-morbidities, and the use of adipose-derived stem cells for future therapies.
adipocytes; obesity; cardiovascular disease; stem cells
The incidence of AD is increasing in parallel with the increase in life expectancy. At the same time the prevalence of metabolic syndrome and obesity is reaching epidemic proportions in western populations. Stress is one of the major inducers of visceral fat and obesity development, underlying accelerated aging processes. Adipose tissue is at present considered as an active endocrine organ, producing important mediators involved in metabolism regulation as well as in inflammatory mechanisms. Insulin and leptin resistance has been related to the dysregulation of energy balance and to the induction of a chronic inflammatory status which have been recognized as important cofactors in cognitive impairment and AD initiation and progression. The aim of this paper is to disclose the correlation between the onset and progression of AD and the stress-induced changes in lifestyle, leading to overnutrition and reduced physical activity, ending with metabolic syndrome and obesity. The involved molecular mechanisms will be briefly discussed, and advisable guide lines for the prevention of AD through lifestyle modifications will be proposed.
The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles – the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.
Abdominal obesity; Atherogenic dyslipidemia; Coronary artery disease; Insulin resistance; Metabolic syndrome; Triglycerides
The obese are at increased risk for cardiovascular disease and type 2 diabetes. However, some who are obese have no metabolic abnormalities. So, it is not adipose tissue per se, but perhaps where it is located that is important for determining metabolic consequences. Regular exercise is known to reduce risk for metabolic disease through numerous mechanisms. The purpose of this report is to highlight some of the efficacy-based data on the effects of exercise (and also a sedentary lifestyle) on abdominal obesity, visceral fat, and metabolic risk. We also discuss how impaired fatty acid oxidation (FAO) in skeletal muscle may be related to both insulin resistance and a contributor to weight gain. In summary, it is evident that exercise in sufficient amounts can lead to substantial decreases in body weight, total body fat, and visceral fat. Additionally, evidence now supports the conclusion that there is a dose–response relationship between exercise amount and these changes, i.e., more exercise leads to additional benefits. Additionally, there are a number of important cardiometabolic risk factors that were most favorably effected by moderate-intensity compared to vigorous-intensity exercise. Unfortunately, it is also apparent that in sedentary middle-aged men and women, short periods of physical inactivity lead to significant weight gain, substantial increases in visceral fat, and further metabolic deterioration. Finally, favorable modulation of mitochondrial oxidative capacity in skeletal muscle by exercise training may reduce a block for complete oxidation of fatty acids in muscle and thereby relieve a block to effective insulin signaling.
Visceral white adipose tissue (WAT) hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity.
C57BL/6 J mice were fed a high-fat diet (HFD) or normal diet (ND) and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery) after 2–4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9) and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14). Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages.
In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of diet-induced obesity.
Adipocytokine dysregulation; Transcriptional response; Adipose tissue; Extracellular matrix; Cathepsin; Fibrosis
It is commonly believed that the pathophysiology of obesity arises from adiposity. In this paper, I forward a complementary explanation; this pathophysiology arises not from adiposity alone, but also from the psychological stress induced by the social stigma associated with being obese.
In this study, I pursue novel lines of evidence to explore the possibility that obesity-associated stigma produces obesity-associated medical conditions. I also entertain alternative hypotheses that might explain the observed relationships.
I forward four lines of evidence supporting the hypothesis that psychological stress plays a role in the adiposity-health association. First, body mass index (BMI) is a strong predictor of serological biomarkers of stress. Second, obesity and stress are linked to the same diseases. Third, body norms appear to be strong determinants of morbidity and mortality among obese persons; obese whites and women – the two groups most affected by weight-related stigma in surveys – disproportionately suffer from excess mortality. Finally, statistical models suggest that the desire to lose weight is an important driver of weight-related morbidity when BMI is held constant.
Obese persons experience a high degree of stress, and this stress plausibly explains a portion of the BMI-health association. Thus, the obesity epidemic may, in part, be driven by social constructs surrounding body image norms.
The worldwide epidemic of obesity has brought cons iderable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.
Obesity and shorter telomeres are commonly associated with elevated risk for age-related diseases and mortality. Whether telomere length (TL) may be associated with obesity or variations in adiposity is not well established. Therefore, we set out to test the hypothesis that TL may be a risk factor for increased adiposity using data from a large population-based cohort study.
Levels of adiposity were assessed in 6 ways (obesity status, body mass index or BMI, the percentage of body fat or % body fat, leptin, visceral and subcutaneous fat mass) in 2,721 elderly subjects (42% black and 58% white). Associations between TL measured in leukocytes at baseline and adiposity traits measured at baseline and 3 of these traits after 7 years of follow-up were tested using regression models adjusting for important covariates. Additionally, we look at weight changes and relative changes in BMI and % body fat between baseline and follow-up.
At baseline, TL was negatively associated with % body fat (β = −0.35 ± 0.09, p = 0.001) and subcutaneous fat (β = −2.66 ± 1.07, p = 0.01), and positively associated with leptin after adjusting for % body fat (β = 0.32 ± 0.14, p = 0.001), but not with obesity, BMI or visceral fat. Prospective analyses showed that longer TL was associated with positive percent change between baseline and 7-year follow-up for both BMI (β = 0.48 ± 0.20, p = 0.01) and % body fat (β = 0.42 ± 0.23, p = 0.05).
Our study suggests that shorter TL may be a risk factor for increased adiposity. Coupling with previous reports on their reversed roles, the relationship between adiposity and TL may be complicated and warrant more prospective studies.
Obesity; telomere length; adiposity; telomeres
The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB1) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB1 mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes.
Circulating oxidized LDL, a marker of oxidative stress, is associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease in adults. However, little is known about its relation to insulin resistance and cardiovascular risk factors in children. The purpose of this study was to assess the relation of oxidative stress, measured by circulating oxidized LDL, with measures of adiposity and insulin resistance in children.
Oxidized LDL, measures of body fatness (body mass index: BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral and subcutaneous fat), insulin resistance with euglycemic insulin clamp (Mlbm), blood pressure, and blood lipids were obtained in 78 children. Oxidized LDL was compared between normal weight children (BMI < 85th percentile) and overweight/obese children (BMI ≥ 85th percentile) and levels were evaluated for associations with body fatness and insulin resistance.
Oxidized LDL levels were significantly higher in overweight/obese vs. normal weight children (p < 0.0001). Oxidized LDL was significantly correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, and abdominal subcutaneous fat (all p-values < 0.0001). Moreover, oxidized LDL was negatively correlated with Mlbm, even after adjustment for adiposity (p < 0.01).
Oxidized LDL is significantly associated with adiposity and with insulin resistance, independent of body fatness, in children. Oxidative stress may be independently related to the development of insulin resistance early in life, especially in obese youth.
Oxidized LDL; obesity; insulin resistance; children
Obesity is now recognised as a worldwide epidemic. The recent International Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF) analysis estimates that approximately 1.0 billion adults are currently overweight and a further 475 million are obese. Obesity has huge psychosocial impact with obese children and adolescents facing discrimination and stigmatization in many areas of their lives leading to body dissatisfaction, low self-esteem and depression. Indeed, obesity is recognised as an important risk factor for the development of several chronic diseases such as hypertension, cancer, asthma and metabolic syndrome. Chronic low grade systemic inflammation is considered as a hallmark of obesity and may possibly explain the link between obesity and chronic disease, in particular the increased incidence, prevalence and severity of asthma in obese individuals. There is now strong evidence for infiltration of immune and inflammatory cells into adipose tissue that drives systemic inflammation and subsequent end organ damage. In addition to adipocytes, the key adipose tissue resident immune cells are macrophages and mast cells. Immunometabolism, as an emerging field of investigation, explores the pivotal role of these immune cells in translating immunological changes to metabolic effects in obesity. Abundance of free fatty acids, along with other inflammatory cytokines shift the balance of metabolic homeostasis to pro-inflammatory status by influencing the development of inflammatory cell lineage, which, further exhibits distinct functional phenotypes. There is emerging evidence for macrophage activation and functional polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1 phenotype of macrophages in obese adipose tissue. Similarly, studies in both obese humans and murine models reveal the pathognomic presence of an increased number of mast cells in visceral adipose tissue. These suggest a possible contribution of mast cells to the unique metabolome of obese asthma. This review examines proposed multilevel interactions between metabolic and immune systems in obese asthmatics that underlie the negative effects of obesity and may offer significant therapeutic promise.
obesity; immunometabolism; macrophages; mast cells; asthma
Obesity is characterized by the abnormal or excessive deposition of fat in the adipose tissue. Its consequences go far beyond adverse metabolic effects on health, causing an increase in oxidative stress, which leads not only to endothelial dysfunction but also to negative effects in relation to periodontitis, because of the increase in proinflammatory cytokines. Thus obesity appears to participate in the multifactorial phenomenon of causality of periodontitis through the increased production of reactive oxygen species. The possible causal relationship between obesity and periodontitis and potential underlying biological mechanisms remain to be established; however, the adipose tissue actively secretes a variety of cytokines and hormones that are involved in inflammatory processes, pointing toward similar pathways involved in the pathophysiology of obesity, periodontitis and related inflammatory diseases. So the aim of this article is to get an overview of the association between obesity and periodontitis and to review adipose-tissue – derived hormones and cytokines that are involved in inflammatory processes and their relationship to periodontitis.
Adipokines; obesity; periodontal disease
There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective.
Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance.
Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy.
There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.
A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity.
To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat.
We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI⩾30 kg m−2) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS+ or CLS− based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLSs), omental (CLSo) and mesenteric (CLSm) adipose depots.
The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS+) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS+ status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved.
In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.
inflammation; obesity; insulin resistance