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Purpose of Review: There is a large inter-individual variability in the magnitude of body weight change that cannot be fully explained by differences in daily energy intake and physical activity levels and that can be attributed to differences in energy metabolism. Measuring the short-term metabolic response to acute changes in energy intake can better uncover this inter-individual variability and quantify the degree of metabolic thriftiness that characterizes an individual's susceptibility to weight gain and resistance to weight loss. This review summarizes the methods used to identify the individual-specific metabolic phenotype (thrifty vs. spendthrift) in research and clinical settings., Recent Findings: The metabolic responses to short-term fasting, protein-imbalanced overfeeding, and mild cold exposure constitute quantitative factors that characterize metabolic thriftiness., Summary: The energy expenditure response to prolonged fasting is considered the most accurate and reproducible measure of metabolic thriftiness, likely because the largest energy deficit best captures interindividual differences in the extent of metabolic slowing. However, all the other dietary/environmental challenges can be used to quantify the degree of thriftiness using whole-room indirect calorimetry. Efforts are underway to identify alternative methods to assess metabolic phenotypes in clinical and outpatient settings such as the hormonal response to low-protein meals., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Circulating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined., Methods: In study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition., Results: After adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06)., Conclusions: Lower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation., Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT00340132, NCT00342732., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Basolo, Ando, Chang, Hollstein, Krakoff, Piaggi and Votruba.)

Objective: This study aimed to assess the relationship between dopamine, a neurotransmitter involved in feeding behavior, and ad libitum energy intake in humans., Methods: Healthy individuals (n = 158; 72 Native American, 50 white, 18 black, and 18 Hispanic participants; BMI: 33 [SD 9] kg/m 2 ; body fat: 33% [SD 9%]) were admitted for two inpatient studies investigating the determinants of ad libitum energy intake and assessed for 3 days using a highly reproducible, computerized vending machine paradigm. Urine was collected for 24 hours during eucaloric conditions prior to the ad libitum feeding period, and urinary dopamine excretion rate was quantified by high-performance liquid chromatography., Results: Urinary dopamine excretion rate was on average 346 ± 106 μg over 24 hours and was positively correlated with BMI (r = 0.28, P < 0.0001). Higher dopamine concentrations were associated with lower cognitive restraint (ρ = -0.25, P = 0.005) and greater total ad libitum energy intake (r = 0.29, P = 0.0002). However, after adjustment for anthropometrics, in black and white cohorts, higher dopamine concentrations were associated with greater total ad libitum energy intake (r = 0.70, P = 0.001 and r = 0.33, P = 0.02, respectively), whereas no associations were observed in Native American or Hispanic cohorts (all P > 0.3)., Conclusions: Higher urinary dopamine concentrations are associated with greater ad libitum energy intake, indicating a role for dopamine in the reward pathway regulating human feeding behavior., (© 2020 The Obesity Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: A greater decrease in 24-hour energy expenditure (EE) during fasting and a smaller increase in 24-hour EE during low-protein overfeeding (metabolic "thrifty" phenotype) predict weight gain. As thyroid hormones (TH) are implicated in energy intake and metabolism, we assessed whether: (i) TH concentrations are altered by 24-hour fasting or overfeeding diets with varying protein content and (ii) diet-related changes in TH correlate with concomitant changes in EE. Methods: Fifty-eight euthyroid healthy subjects with normal glucose regulation underwent 24-hour dietary interventions including fasting, eucaloric feeding, and five overfeeding diets in a crossover design within a whole-room indirect calorimeter to measure the 24-hour EE. Overfeeding diets (200% of energy requirements) included three diets with 20% protein, one diet with 3% protein (low-protein overfeeding diet [LPF]: 46% fat), and one diet with 30% protein (high-protein overfeeding diet [HPF]: 44% fat, n  = 51). Plasma free thyroxine (fT4), free triiodothyronine (fT3), and fibroblast growth factor 21 (FGF21) concentrations were measured after overnight fast the morning of and after each diet. Results: On average, fT4 increased by 8% (+0.10 ng/dL, 95% confidence interval [CI 0.07-0.13], p  < 0.0001) and fT3 decreased by 6% (-0.17 pg/mL [CI -0.27 to -0.07], p  = 0.001) after 24-hour fasting, whereas both fT4 and fT3 decreased by 5% (-0.07 ng/dL [CI -0.11 to -0.04], p  < 0.0001) and 4% (-0.14 pg/mL [CI -0.24 to -0.04], p  = 0.008) following HPF, respectively. Greater decreases in fT3 after HPF are associated with larger decreases in FGF21 ( r  = 0.40, p  = 0.005). Following LPF, the mean fT3 increased by 6% (+0.14 pg/mL [CI 0.05-0.2], p  = 0.003) with no change in fT4 ( p  = 0.7). No changes in TH were observed after normal-protein overfeeding diets (all p  > 0.1). No associations were observed between TH concentrations and diet-related changes in 24-hour EE during any diet (all p  > 0.07). Conclusions: Acute (200%) short-term (24 hours) changes in food intake induce small changes in TH concentrations only after diets with low (0% fasting and 3% protein overfeeding) or high (30% protein overfeeding) protein content. The fT3-FGF21 association after high-protein overfeeding suggests a role for TH in inhibiting FGF21 secretion by the liver during protein excess. These results indicate that TH are involved in protein metabolism; however, they do not mediate the short-term EE response to diets that characterize the metabolic phenotypes and determine the individual susceptibility to weight gain.