Regulators of Food Intake

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

Energy intake and dietary macronutrient composition is the most difficult part of the energy balance equation to measure. In a natural history study of factors which predict food intake and using an inpatient computerized vending machine system, food intake has been measured over 300 individuals. In individuals undergoing the study more than once the intra-class correlation coefficient is very high (r=0.9) indicating that these studies although performed in an inpatient setting are very reproducible. This study has demonstrated that higher respiratory quotient. And higher carbohydrate oxidation are associated with energy intake. We have also demonstrated that both fat free mass (adjusted for height) and 24 hour energy expenditure are associated with ad libitum food intake. Even after adjustment for fat free mass, the residual of energy expenditure was still associated with energy intake. In mediation analysis, energy expenditure accounts for over 80% of the explained variance in energy intake indicating that energy expenditure rather than fat free mass drives energy intake. Thus, increases in metabolic rate (as a weight loss intervention) may have the paradoxical effect of stimulating excess caloric intake. In fact, in further analyses, we have found that energy intake adjusted for energy expenditure predicts weight gain. We are investigating this energy sensing link further in a protocol which investigates if increased energy expenditure (as induced by cold) will lead to increases in food intake. In this approved protocol we are investigating also the timing of the increase in energy expenditure, whether this energy sensing occurs immediately or following the cold induced increase in EE. This protocol is currently actively recruiting participants. Using this ad libitum vending machine model, we have found that calories from soda intake predicted future weight gain indicating a role for sweetened beverages as contributeor to the current obesity epidemic. In work elucidating hormonal associations with ad libitum intake, we found that those with higher fasting fibroblast growth factor 21 concentrations consume less soda. We also found that higher fasting GLP-1 concentrations were associated with lower carbohydrate and lower intake of high simple sugar/high fat foods indicating a role for GLP-1 in rewards based food selection. Higher urinary dopamine also a potential marker of reward based food selection was associated with greater drive to eat and overall increased energy intake. In an effort to understand behavioral and psychosocial factors, we have also investigated whether socioeconomic status and food insecurity are associated with energy intake. We found that those with higher food insecurity scores, eat more during the ad libitum period. Moreover, individuals with food insecurity have metabolic risk factors for increased energy intake and weight gain namely higher 24h RQ, higher carbohydrate oxidation and lower lipid oxidation rates. We have continued investigating novel dietary biomarkers in our study investigating stable isotopes ratios. In this study, individuals (n=32) consumed diets over 3 months while domiciled on our inpatient unit. The study was a multi-factorial design in which dietary pattern varied by meat, soda and fish content. Plasma (collected every 2 weeks) and hair, were analyzed for changes in the stable isotopes C13 and N15. In both plasma and hair, carbon isotope enrichment was associated with meat and soda intake, but more strongly with meat intake, while nitrogen isotope enrichment was associated with fish intake. Of interest, pre-intervention isotope ratios were associated with post-intervention ratios indicating that even after 12 weeks of a stable diet, that turnover was incomplete. Stable isotope ratios in specific amino acids and fatty acids may provide even more specific food signatures. We found that carbon isotope ratio (CIR) in plasma alanine had a high sensitivity and specificity for soda intake, while CIR for leucine demonstrated the same for meat intake. We have also found specific long chain fatty acid signatures that denote meat intake. We are currently investigating whether we can identify plasma metabolomic signatures that are associated with dietary patterns, and how these metabolomic signatures may be related to shifts in the gut microbiome. In this study, we also found important changes in metabolism notably that those who consumed fish for 12 weeks increased their 24h energy expenditure while those who consumed soda decreased their 24h energy expenditure indicating a role of diet pattern (or quality) on EE independent of macronutrient composition. We have received NIH IRB approval to begin a follow-up study investigating how dose of soda intake over a 12 week period affects stable isotope ratios, additional dietary biomarkers (long chain fatty acid profiles, metabolomics), gut microbiome and energy expenditure. An understudied component of food intake, is regulation of thirst and thirst perception. Our clinical trial comparing water intake and thirst perception in lean versus individuals with obesity following a 24 hour fast without fluid intake and a 3% saline challenge found that adjusted for body size, lean and obese individuals drank the same amount of water following these challenges, but thirst perception in obese was lower as was their copeptin response to both challenges. Leptin may mediate this lower co-peptin response but we have not found additional evidence that other hormones purportedly involved in water balance (aldosterone, atrial and brain natriuretic peptide or apelin) differ between lean and obese individuals during these tests. Adherence is also a crucial component of success for diet induced weight loss. We completed a study investigating whether dietary adherence differed in lean versus individuals with obesity on weight maintaining versus calorie reduction diet. We found that there was no difference in adherence of hunger measures between the groups. These results indicate that difficulty with dietary adherence is not characteristic of individuals with obesity nor driven by hunger associated with dieting. In this study we used ecological momentary assessment (EMA) as a daily adherence measure. These measures were sent randomly to participants twice daily. We found that affect affected adherence as measured by EMA, such that those with overall negative affect were less adherent. This has important implications for identifying risk factors for adherence to dietary interventions.