Inherent individual variability in substrate oxidation may predispose to obesity. In this study, we found that among premenopausal obesity-prone women, high NSRQ predicted ΔFM independent of energy balance, circulating insulin, and insulin sensitivity. No association was observed between fat accumulation and other RQ values, including fasting, sleeping, and 24-hour RQ. These results suggest that low postprandial fat oxidation and/or elevated post-prandial carbohydrate oxidation may predispose certain women to weight gain and excess adiposity.
Results of this study advance existing evidence about the relationship between RQ and weight gain. Although some previous studies have reported positive associations between weight gain and either fasting or 24-hour RQ (4
), we have reported no correlation (10
). Incongruent reports may reflect population-specific differences in energy metabolism. Notably, several studies supporting an association between weight gain and high 24-hour RQ were conducted among Pima Indians (5
), and recent genetic studies have identified Single Nucleotide Polymorphisms specific to this population that may underlie these findings (23
). Discrepancies in the literature are also likely due to variable control for dietary factors known to acutely influence RQ. For example, it is well-established that either positive energy balance or high carbohydrate intake can transiently elevate RQ (3
). However, few studies relating RQ to weight gain have accounted for differences in macronutrient intake and/or energy balance between subjects. In the present study, all participants were provided with food for 4 weeks prior to RQ measurement in order to ensure uniform macronutrient intake and stable body weight. During their stay in the respiratory chamber, diet was controlled to provide a standard macronutrient profile and kilocalories for energy balance. Additionally, we used statistical methods to adjust for energy balance inside the respiratory chamber.
Individual differences in circulating insulin and/or insulin sensitivity may also confound reported relationships between weight gain and RQ. Circulating insulin suppresses lipid oxidation and facilitates fat storage (13
). Among a cohort of 293 Caucasian women, Nagy et al. demonstrated that fasting insulin was inversely associated with fat oxidation (14
). Similarly, Weinsier et al. reported that fasting insulin predicted 4-year weight gain among Caucasian, postmenopausal, normoglycemic women (10
). Insulin sensitivity has been associated with fat accumulation in some (15
), but not all (24
) studies. Consistent with these findings, SI
among our sample showed a trend toward positive association with ΔFM after 2 years (r = 0.316, p = 0.073). By statistically adjusting for fasting insulin, AIRg, and SI
, we assured that the observed relationship between ΔFM and NSRQ was not influenced by confounding relationships between insulin and RQ or FM. The final multiple linear regression model that included NSRQ, energy balance, and SI
explained ~23% of the variance in ΔFM after 2 years.
Our previous analyses among African American and Caucasian women with tight dietary control also identified no relationship between weight gain and other RQ measures, including fasting, 24-hour, or sleeping RQ (10
). These three RQ measures encompass periods of the day when RQ should signify fat oxidation of endogenous free fatty acids. NSRQ, however, is measured specifically during the non-sleeping period in the respiratory chamber and would correspond to the typical, physiological postprandial period. Sources of variability in NSRQ may include endocrine factors such as concentrations of estrogen (25
) or thyroid function (26
). In the present study, NSRQ distinctively and independently predicted fat mass accrual. High NSRQ may represent suppressed oxidation of dietary lipid and/or an enhanced ability to switch to carbohydrate oxidation in response to a mixed substrate meal. If lipid oxidation is suppressed, these individuals may be less able to increase fat oxidation after dietary fat intake, and they may therefore be prone to store fat as adipose leading to a partitioning of energy towards fat mass at the expense of lean mass. Moreover, previous studies have suggested that greater carbohydrate oxidation and lesser fat oxidation may predispose certain individuals to store less glycogen and therefore experience more hunger (22
). This increased hunger may lead to chronic positive energy imbalance and gain in body fat.
The study was strengthened by robust measures for all variables, including IVGTT for insulin sensitivity, chamber calorimetry for RQ assessments, and DXA for body composition. Strengths of this study also included tight control of dietary intake prior to and during RQ measurements. Despite attempts to achieve zero energy balance within the chamber, variability in energy balance may present a potential confounder. Therefore, all models included statistical adjustment for energy balance. Efforts were made to minimize confounders by the homogeneity of the cohort. However, because we examined a very specific subject population of normal glucose tolerant, premenopausal women of only African American and European American ethnicity, it is impossible to extrapolate these findings to other ethnicities, men, older women, never-overweight individuals, or those with impaired glucose tolerance. Given the limited sample size and overall significance of the models, results should be interpreted with caution and repeated in larger samples.
In conclusion, the current study revealed that among obesity-prone premenopausal women, NSRQ uniquely predicted ΔFM independent of energy balance and insulin sensitivity. Because all of the women in our cohort reported a family history of overweight or obesity in a first degree relative, high NSRQ may be a marker for non-modifiable genetic factors affecting their capacity to oxidize lipid and carbohydrate. Studies are needed to determine whether these women may experience more success with weight maintenance by modifying their food choices to reduce fat intake or by modifying their physical activity to enhance fat oxidation.