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. We have also demonstrated that both fat free mass (adjusted for height) and 24-hour energy expenditure are associated with ad libitum food 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 were able to quantify how much intake affects the protective effect of EE on weight gain calculating that for every 0.46kg/100 kcal higher EE there is a counterbalance of -23 kg/100 kcal from drive to increased intake. We are investigating this energy sensing link further in a protocol which investigates if changes in energy expenditure (as induced by fasting and cold exposure) will lead to increases in food intake. 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 contributor to the current obesity epidemic. In work elucidating hormonal associations with ad libitum intake, we found that participants 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 a potential marker of reward-based food selection was associated with greater drive to eat and increased energy intake. We have also demonstrated that dietary protein has a negative regulatory effect on short term (meal to meal) protein and total calorie intake, but not on daily intake. 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, lower lipid oxidation rates and lower fasting concentrations of the appetite suppressing hormone, GLP-1. We have continued investigating novel dietary biomarkers in our study investigating stable isotopes ratios. 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. 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 also found that amino acid nitrogen isotope ratios (NIR) can denote diet patterns. NIR in amino acid leucine denoted fish intake, while NIR in amino acid threonine was lower in meat and fish intake. We have also found specific long chain fatty acid signatures that denote meat intake. The CIR of plasma saturated and mono-unsaturated fatty acids are sensitive and specific measures of dietary meat intake, but not SSB or fish intake. We measured the total fatty acid concentration in each participant as well. Increased relative abundances of plasma odd-chain fatty acids i-15:0, 17:0, and 17:1 were associated with meat intake, and higher relative abundances of plasma EPA and DHA (20:5n-3 and 22:6n-3) were associated with fish. We have performed 16sRNA analysis of collected stool specimens prior to and following each diet period and are currently investigating whether we can identify changes in gut microbiome by dietary exposure. 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. However, we did find that overall levels of perceived stress, anhedonia and food insecurity measured prior to the diet period predicted lower adherence independent of percent body fat. 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. Thus, we have identified important and possibly modifiable determinants of adherence. We have also recently started an on-line study investigating how the COVID-19 pandemic has affected eating behaviors and weight gain. The goal of the study is to recruit participants across the world who answer questions about COVID, eating behavior and weight history. Participants are asked to complete questionnaires monthly for 12 months. There is also a opportunity to participate in an ecological momentary assessment substudy that will assess more immediate daily impacts of COVID pandemic and eating behavior.