Tracy J. Horton

The effects of short-term overfeeding on energy expenditure and nutrient oxidation in obesity-prone and obesity-resistant individuals

Objective:The roles that energy expenditure (EE) and nutrient oxidation play in a predisposition for weight gain in humans remains unclear.Subjects:We measured EE and respiratory exchange ratio (RER) in non-obese obesity-prone (OP; n=22) and obesity-resistant (OR; n=30) men and women following a eucaloric (EU) diet and after 3 days of overfeeding (1.4 × basal energy).Results:Twenty-four hour EE, adjusted for fat-free mass and sex, measured while consuming a EU diet was not different between OP and OR subjects (2367±80 vs 2285±98 kcals; P=0.53). Following overfeeding, EE increased in both OP and OR (OP: 2506±63.7, P<0.01; OR: 2386±99 kcals, P<0.05). Overfeeding resulted in an increase in 24-hour RER (OP: 0.857±0.01 to 0.893±0.01, P=0.01; OR: 0.852±0.01 to 0.886±0.01, P=0.005), with no difference between groups in either the EU or overfeeding conditions (P>0.05). Nighttime RER (∼10pm–6:30am) did not change with overfeeding in OR (0.823±0.02 vs 0.837±0.01, P=0.29), but increased significantly in OP subjects (0.798±0.15 to 0.839±0.15, P<0.05), suggesting that fat oxidation during the night was downregulated to a greater extent in OP subjects following a brief period of overfeeding, as compared with OR subjects who appeared to maintain their usual rate of fat oxidation. Protein oxidation increased significantly in both OP (P<0.001) and OR (P<0.01) with overfeeding, with no differences between OP and OR.Conclusion:These results support the idea that overfeeding a mixed diet results in increases in EE and RER, but these increases in EE and RER are likely not responsible for obesity resistance. Adaptive responses to overfeeding that occur during the night may have a role in opposing weight gain.

Greater systemic lipolysis in women compared with men during moderate-dose infusion of epinephrine and/or norepinephrine

Women have lower circulating catecholamine levels during metabolic perturbations, such as exercise or hypoglycemia, but similar rates of systemic lipolysis. This suggests women may be more sensitive to the lipolytic action of catecholamines, while maintaining similar glucoregulatory effects. The aim of the present study, therefore, was to determine whether women have higher rates of systemic lipolysis compared with men in response to matched peripheral infusion of catecholamines, but similar rates of glucose turnover. Healthy, nonobese women (n = 11) and men (n = 10) were recruited and studied on 3 separate days with the following infusions: epinephrine (Epi), norepinephrine (NE), or the two combined. Tracer infusions of glycerol and glucose were used to determine systemic lipolysis and glucose turnover, respectively. Following basal measurements of substrate kinetics, the catecholamine infusion commenced, and measures of substrate kinetics continued for 60 min. Catecholamine concentrations were similarly elevated in women and men during each infusion: Epi, 182-197 pg/ml and NE, 417-507 pg/ml. There was a significant sex difference in glycerol rate of appearance and rate of disappearance with the catecholamine infusions (P < 0.0001), mainly due to a significantly greater glycerol turnover during the first 30 min of each infusion: glycerol rate of appearance during Epi was only 268 +/- 18 vs. 206 +/- 21 micromol/min in women and men, respectively; during NE, only 173 +/- 13 vs. 153 +/- 17 micromol/min, and during Epi+NE, 303 +/- 24 vs. 257 +/- 21 micromol/min. No sex differences were observed in glucose kinetics under any condition. In conclusion, these data suggest that women are more sensitive to the lipolytic action of catecholamines, but have no difference in their glucoregulatory response. Thus the lower catcholamine levels observed in women vs. men during exercise and other metabolic perturbations may allow women to maintain a similar or greater level of lipid mobilization while minimizing changes in glucose turnover.

Skeletal muscle munc18c and syntaxin 4 in human obesity

BackgroundAnimal and cell culture data suggest a critical role for Munc18c and Syntaxin 4 proteins in insulin mediated glucose transport in skeletal muscle, but no studies have been published in humans.MethodsWe investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects. Healthy lean (n = 14; age = 28.0 +/- 1.4 yr; BMI = 22.8 +/- 0.42 kg/m2) and obese subjects (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5 kg/m2) were studied twice following a 12 and 48 hr fast. Skeletal muscle biopsies were obtained before a 3 hr 40 mU/m2/min hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose infusion.ResultsGlucose rate of disappearance (Rd) during the clamp was lower in obese vs. lean subjects after the 12 hr fast (obese: 6.25 +/- 0.67 vs. lean: 9.42 +/- 1.1 mg/kgFFM/min, p = 0.007), and decreased significantly in both groups after the 48 hr fast (obese 3.49 +/- 0.31 vs. lean: 3.91 +/- 0.42 mg/kgFFM/min, p = 0.002). Munc18c content was not significantly different between lean and obese subjects after the 12 hour fast, and decreased after the 48 hr fast in both groups (p = 0.013). Syntaxin 4 content was not altered by obesity or fasting duration. There was a strong positive relationship between plasma glucose concentration and Munc18c content in lean and obese subjects during both 12 and 48 hr fasts (R2 = 0.447, p = 0.0015). Significant negative relationships were also found between Munc18c and FFA (p = 0.041), beta-hydroxybutyrate (p = 0.039), and skeletal muscle AKT content (p = 0.035) in lean and obese subjects.ConclusionThese data indicate Munc18c and Syntaxin 4 are present in human skeletal muscle. Munc18c content was not significantly different between lean and obese subjects, and is therefore unlikely to explain obesity-induced insulin resistance. Munc18c content decreased after prolonged fasting in lean and obese subjects concurrently with reduced insulin action. These data suggest changes in Munc18c content in skeletal muscle are associated with short-term changes in insulin action in humans.

The effects of sex, metabolic syndrome and exercise on postprandial lipemia

OBJECTIVE Exercise has been suggested to have cardioprotective benefits due to a lowering of postprandial triglycerides (PPTG). We hypothesized that a morning exercise bout would significantly lower PPTG measured over a full day, in response to moderate fat meals (35% energy) in men more so than women, and in metabolic syndrome (MetS) relative to normal weight (NW) individuals. MATERIALS/METHODS Participants completed two randomized study days; one control and one exercise day (60 min of morning exercise, 60% VO(2peak)). Meals were consumed at breakfast, lunch and dinner with the energy expended during exercise replaced on the active day. The areas (AUC) and incremental areas (IAUC) under the curve were calculated for total triglycerides, total cholesterol and other metabolites. RESULTS Exercise did not significantly change the PPTG AUC & IAUC overall, or within, or between, each sex or group (NW and MetS). Exercise induced a 30% decrease in total cholesterol IAUC (p=0.003) in NW subjects. Overall, women had a lower IAUC for PPTG compared to men (p=0.037), with the greatest difference between MetS women and MetS men, due to a sustained drop in TG after lunch in the women. This suggests that PP, rather than fasting, lipid analyses may be particularly important when evaluating sex differences in metabolic risk. CONCLUSIONS With energy replacement, moderate morning exercise did not result in a significant decrease in PPTG excursions. Exercise did elicit a significant decrease in PP cholesterol levels in NW subjects, suggesting a potential mechanism for the cardioprotective effects of exercise.

Effects of short‐term sex steroid suppression on dietary fat storage patterns in healthy males

Hypogonadism in males is associated with increased body fat and altered postprandial metabolism, but mechanisms remain poorly understood. Using a cross‐over study design, we investigated the effects of short‐term sex hormone suppression with or without testosterone add‐back on postprandial metabolism and the fate of dietary fat. Eleven healthy males (age: 29 ± 4.5 year; BMI: 26.3 ± 2.1 kg/m2) completed two 7‐day study phases during which hormone levels were altered pharmacologically to produce a low sex hormone condition (gonadotropin releasing hormone antagonist, aromatase inhibitor, and placebo gel) or a testosterone add‐back condition (testosterone gel). Following 7 days of therapy, subjects were administered an inpatient test meal containing 50 μCi of [1‐14C] oleic acid. Plasma samples were collected hourly for 5 h to assess postprandial responses. Energy metabolism (indirect calorimetry) and dietary fat oxidation (14CO2 in breath) were assessed at 1, 3, 5, 13.5, and 24 h following the test meal. Abdominal and femoral adipose biopsies were taken 24 h after the test meal to determine uptake of the labeled lipid. Postprandial glucose, insulin, free‐fatty acid, and triglyceride responses were not different between conditions (P > 0.05). Whole‐body energy metabolism was also not different between conditions at any time point (P > 0.05). Dietary fat oxidation trended lower (P = 0.12) and the relative uptake of 14C labeled lipid into femoral adipose tissue was greater (P = 0.03) in the low hormone condition. Short‐term hormone suppression did not affect energy expenditure or postprandial metabolism, but contributed to greater relative storage of dietary fat in the femoral depot. ClinicalTrials.gov Identifier: NCT03289559.