Effects of 3 diets with various calcium contents on 24-h energy expenditure, fat oxidation, and adipose tissue message RNA expression of lipid metabolism-related proteins.

BACKGROUND: Evidence from molecular and animal research and epidemiologic investigations indicates that calcium intake may be inversely related to body weight, possibly through alterations in 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] metabolism. OBJECTIVE: We tested whether energy and substrate metabolism and adipose tissue enzyme messenger RNA (mRNA) expression can be altered by dietary calcium intake in healthy, nonobese, human volunteers consuming an isocaloric diet. DESIGN: Twelve healthy men [age: 28 +/- 2 y; body mass index (BMI; in kg/m(2)): 25.2 +/- 06] received 3 isocaloric diets [high calcium (1259 +/- 9 mg/d), high dairy (high/high); high calcium (1259 +/- 9 mg/d), low dairy (high/low); and low calcium (349 +/- 8 mg/d), low dairy (low/low)] in a randomized crossover design. At the end of the 7-d dietary periods, 24-h energy expenditure and substrate metabolism were measured, and fat biopsy specimens were obtained to determine mRNA expression in genes involved in the lipolytic and lipogenic pathways. RESULTS: The 24-h energy expenditure was 11.8 +/- 0.3, 11.6 +/- 0.3, and 11.7 +/- 0.3 MJ/24 h in the high/high, high/low, and low/low conditions, respectively. Fat oxidation in these conditions was 108 +/- 7, 105 +/- 9, and 100 +/- 6 g/24 h. These differences were not statistically significant. mRNA concentrations of UCP2, FAS, GPDH2, HSL, and PPARG did not differ significantly. Serum 1,25(OH)(2)D(3) concentrations changed from 175 +/- 16 to 138 +/- 15, 181 +/- 23 to 159 +/- 19, and 164 +/- 13 to 198 +/- 19 pmol/L in the high/high, high/low, and low/low conditions, respectively, and was significantly different between the high/high and low/low conditions (P < 0.05). CONCLUSION: Altering the dietary calcium content for 7 d does not influence substrate metabolism, energy metabolism, or gene expression in proteins related to fat metabolism, despite significant changes in 1,25(OH)(2)D(3) concentrations.

Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy expenditure in obese men.

OBJECTIVE: Our objective was to investigate the thermogenic efficacy of single oral doses of the novel beta(3)-adrenergic receptor agonist L-796568 [(R )-N -[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]-phenyl]-4-[4-[4-(trifluoromethyl)phenyl]thiazol-2-yl]-benzenesulfonamide, dihydrochloride] in humans. METHODS: Twelve healthy overweight to obese men participated in this 2-center, 3-period, randomized, placebo-controlled, crossover trial. In each period subjects received 250 mg L-796568, 1000 mg L-796568, or placebo. Energy expenditure and respiratory quotient were determined by indirect calorimetry; blood samples were taken; and ear temperature, heart rate, and blood pressure were measured at baseline and during the 4-hour period after administration. RESULTS: Energy expenditure increased significantly after the 1000-mg dose (about 8%) and this was accompanied by an increase in plasma glycerol and free fatty acid concentrations. Systolic blood pressure also increased significantly. No changes in heart rate, diastolic blood pressure, ear temperature, plasma catecholamine, potassium, or leptin were found. CONCLUSIONS: Single-dose administration of 1000 mg of the novel beta(3)-adrenergic receptor agonist L-796568 increased lipolysis and energy expenditure in overweight men. This is the first study to show such an effect of beta(3)-adrenergic receptor agonists in humans without significant evidence for beta(2)-adrenergic receptor involvement.

Differential valine metabolism in adipose tissue of low and high fat-oxidizing obese subjects.

Differences in fat metabolism are of importance in relation to energy balance. Low fat-oxidizers (LFO) are thought to be more prone for developing obesity. We studied whether LFO have different fasting adipose tissue (AT) protein profiles than high fat-oxidizers (HFO). Six LFO and six HFO subjects were selected from an obese group (n = 99, body mass index>30 kg/m(2) ) taking part in a multi-center study (Nutrient-Gene interaction in human obesity) based on the postprandial fat oxidation capacity after a high fat load. AT protein profiles were studied by 2-DE. Differential proteins were clustered with MAPPfinder according to their function. Protein profiles of purified blood cells and adipocytes served to confine the comparison to adipocyte-specific proteins in AT profiles of LFO and HFO subjects. LFO had increased mitochondrial ROS scavengers possibly related to long-chain unsaturated fatty acid-induced increases in mitochondrial ROS-production. Carbohydrate oxidation seemed to be reduced since expression of several proteins from the glycolysis pathway was lower in LFO. Up-regulation of the valine catabolism at the level of methylmalonate-semialdehyde dehydrogenase appeared to be (part of) the compensatory mechanism. In conclusion, the fasting AT protein profile of LFO and HFO differ at the level of ROS scavenging, the glycolysis pathway and valine metabolism.

Intramyocellular lipid and glycogen content are reduced following resistance exercise in untrained healthy males.

Resistance exercise has recently been shown to improve whole-body insulin sensitivity in healthy males. Whether this is accompanied by an exercise-induced decline in skeletal muscle glycogen and/or lipid content remains to be established. In the present study, we determined fibre-type-specific changes in skeletal muscle substrate content following a single resistance exercise session. After an overnight fast, eight untrained healthy lean males participated in a approximately 45 min resistance exercise session. Muscle biopsies were collected before, following cessation of exercise, and after 30 and 120 min of post-exercise recovery. Subjects remained fasted throughout the test. Conventional light and (immuno)fluorescence microscopy were applied to assess fibre-type-specific changes in intramyocellular triacylglycerol (IMTG) and glycogen content. A significant 27+/-7% net decline in IMTG content was observed in the type I muscle fibres (P<0.05), with no net changes in the type IIa and IIx fibres. Muscle glycogen content decreased with 23+/-6, 40+/-7 and 44+/-7% in the type I, IIa and IIx muscle fibres, respectively (P<0.05). Fibre-type-specific changes in intramyocellular lipid and/or glycogen content correlated well with muscle fibre-type oxidative capacity. During post-exercise recovery, type I muscle fibre lipid content returned to pre-exercise levels within 120 min. No changes in muscle glycogen content were observed during recovery. We conclude that intramyocellular lipid and glycogen stores are readily used during resistance exercise and this is likely associated with the reported increase in whole-body insulin sensitivity following resistance exercise.

The effects of increasing serum calcitriol on energy and fat metabolism and gene expression.

OBJECTIVE: Evidence from a number of investigations indicates that calcium intake could be inversely related to body weight through alterations in the 1,25-OH(2)-D(3) metabolism. The objective of this study was to test whether energy and substrate metabolism and adipose tissue enzyme mRNA expression can be altered by changes in serum 1,25-OH(2)-D(3) through oral cholecalciferol supplementation in non-obese human subjects. RESEARCH METHODS AND PROCEDURES: An intervention study was used with a treatment period of 7 days. During this intervention, energy expenditure (EE) and substrate metabolism were measured using indirect calorimetry at t = 0, 1, 3, and 7 days, and blood samples were obtained at t = -1, 0, 1, 2, 3, 5 and 7 days. Fat biopsies were obtained at t = 0 and 7 days for determination of expression of genes involved in lipolytic and lipogenic pathways. Subjects from the general community were studied in an ambulatory setting at a university hospital. Ten healthy young men (age, 28 +/- 3 years; BMI, 25.5 +/- 0.5 kg/m(2)) were recruited by local announcement, and all completed the study. All subjects received 2000 IU cholecalciferol/d for 7 days, and they were instructed to consume a low-cholecalciferol, low-calcium diet. EE, fat oxidation, and adipose tissue enzyme mRNA were the main outcome measures. RESULTS: Despite a significant increase in serum 1,25-OH(2)-D(3) concentration at t = 5 and 7 days, no significant differences in substrate and energy metabolism nor mRNA concentrations of different lipid metabolism-related proteins were observed. DISCUSSION: Seven-day supplementation with 2000 IU cholecalciferol/d together with a decrease in dietary calcium intake does not affect EE or substrate metabolism nor gene expression of proteins related to fat metabolism, despite a significant increase in serum 1,25-OH(2)-D(3) concentration.

A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men.

The aim of the present study was to determine whether a single session of resistance exercise improves whole-body insulin sensitivity in healthy men for up to 24 h. Twelve male subjects (23 +/- 1 years) were studied over a period of 4 days during which they consumed a standardized diet, providing 0.16 +/- 0.01 MJ.kg(-1).day(-1) containing 15 +/- 0.1 energy% (En%) protein, 29 +/ -0.1 En% fat and 55 +/- 0.3 En% carbohydrate. Insulin sensitivity was determined 24 h before and 24 h after a single resistance exercise session (8 sets of 10 repetitions at 75% of 1 repetition maximum for two leg exercise tasks) using an intravenous insulin tolerance test. Insulin sensitivity index was calculated by the decline in arterial blood glucose concentration following intravenous administration of a single bolus of human insulin (0.075 IU.kg(-1) fat free mass). Basal glucose and insulin concentrations were not changed up to 24 h after the resistance exercise. However, a substantial 13+/-5% improvement in whole-body insulin sensitivity was observed, 24 h after the resistance exercise (P < 0.05). This study shows that even a single session of resistance exercise improves whole-body insulin sensitivity for up to 24 h in healthy men, which is consistent with earlier observations following endurance exercise tasks.