Regulators of Food Intake

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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.The component of respiratory quotient which best predicted food intake was higher carbohydrate oxidation indicating a role for carbohydrate (likely glycogen) balance in the regulation of short term food intake. We have also demonstrated that both fat free mass (adjusted for height) and 24 hour energy expenditure are associated with ad libitum food intakeEven 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 have begun 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. We have also recently found that individuals who select a higher percentage of foods in high simple sugar/high fat content category gain more weight. In an attempt to understand hormonal underpinnings for energy intake macronutrient selection, we investigated the role of plasma GLP-1, FGF21 urinary dopamine concentrations on food selection. We found that increased 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 fasting FGF21 is also associated with lower soda intake. Urinary dopamine 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 indicating an important psychosocial component is at work in determining calorie intake. We have completed our study investigating stable isotopes as biomarkers for dietary patterns. Individuals (n=32) consumed diets over 3 months in a multi-factorial design which 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. We also looked at carbon isotope ratios (CIR) in amino acids and found CIR of plasma alanine had a high sensitivity and specificity for soda intake, while CIR for leucine demonstrated the same for meat intake. In this study, we also found 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 metabolism independent of macronutrient composition. We are continuing perform dietary pattern analyses of CIR and bulk assessment for medium and long chaing fatty acid profiles measured in plasma and adipose tissue. We are also investigatingplasma metabolomic signatures for each diet and linking these metabolomic signature with changes in structure of the gut microbiome. We have submitted the next phase of this study for scientific review, which will investigate whether bulk and amino acid specific CIRs can identify different doses of soda intake on a weight maintaining, macronutrient stable background. An understudied component of food intake, is regulation of thirst and thirst perception. We completed a 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. 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. We are currently analyzing the role of additional hormones that may affect thirst perception and water intake. Adherence is also a crucial component of success for diet induced weight loss. We investigated 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.