Beta-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women.

Continuous respiratory exchange measurements were performed in nine obese and eight lean women for 1 h before, 3 h during, and 1 h after the intravenous administration of a nutrient mixture infused at twice the postabsorptive resting energy expenditure (REE). This experiment was conducted without or with beta-adrenergic blockade (iv propranolol). Propranolol administration did not change the postabsorptive REE [i.e., 1.03 +/- 0.07 before vs. 1.01 +/- 0.02 kcal/min after administration in lean women and 1.16 +/- 0.04 vs. 1.15 +/- 0.03 kcal/min (NS) in obese women]. The mean overall thermogenic response expressed as a percentage of the infused energy was similar in both groups and was not significantly blunted after propranolol infusion [6.9 +/- 0.4 vs. 5.9 +/- 0.6% in the lean women and 7.5 +/- 0.5 vs. 7.1 +/- 0.6% (NS) in the obese women]. During beta-adrenergic blockade the rate of lipid oxidation decreased in the lean group but was unchanged in the obese group and the glycemic response to nutrient administration was significantly higher in both groups than without propranolol. It is concluded that beta-adrenergic blockade has no effect on REE and on intravenous nutrient-induced thermogenesis in both lean and obese women.

Thermogenesis in obese women: effect of fructose vs. glucose added to a meal.

To assess the effect of a fructose meal on resting energy expenditure (EE), indirect calorimetry was used in 23 women (10 lean and 13 obese) for 30 min before and 6 h after the ingestion of a mixed meal containing 20% protein, 33% fat, and either 75 g glucose or 75 g fructose as carbohydrate source (47%). Expressed as a percentage of the energy content of the meal, the thermogenic response to the fructose meal was significantly greater (10.2 +/- 0.5%) than that of the glucose meal (8.4 +/- 0.4%, P less than 0.01). This difference was still apparent when the lean and obese women were considered separately. The mean respiratory quotient during the 6-h postprandial period was significantly greater (P less than 0.01) for the fructose (0.85 +/- 0.01) than for the glucose meal (0.83 +/- 0.01) in the combined subjects. In addition, cumulative carbohydrate oxidation was significantly greater after the fructose than after the glucose meal (51.1 +/- 2.3 vs. 40.9 +/- 2.0 g/6 h, respectively, P less than 0.01). Only small changes were observed in postprandial plasma levels of glucose and insulin after the fructose meal, but the plasma levels of lactate increased more with fructose than with the glucose meal. These results suggest that there might be some advantages (higher thermogenesis and carbohydrate oxidations) in using fructose as part of the carbohydrate source in diet of people with obesity and/or insulin resistance.

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding of diet-induced thermogenesis in adult mouse offspring

Purpose Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Methods Female MF-1 mice were fed a normal protein (NP, 18 % casein) or a protein-restricted (PR, 9 % casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45 % kcal fat) or standard chow (C, 7 % kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7–11 per group). Results PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P < 0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P < 0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P < 0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. Conclusions These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.

Distinct subsets of hypothalamic genes are modulated by two different thermogenesis-inducing stimuli

Obesity results from an imbalance between food intake and energy expenditure, two vital functions that are tightly controlled by specialized neurons of the hypothalamus. The complex mechanisms that integrate these two functions are only beginning to be deciphered. The objective of this study was to determine the effect of two thermogenesis-inducing conditions, i.e., ingestion of a high-fat (HF) diet and exposure to cold environment, on the expression of 1,176 genes in the hypothalamus of Wistar rats. Hypothalamic gene expression was evaluated using a cDNA macroarray approach. mRNA and protein expressions were determined by reverse-transcription PCR (RT-PCR) and immunoblot. Cold exposure led to an increased expression of 43 genes and to a reduced expression of four genes. HF diet promoted an increased expression of 90 genes and a reduced expression of 78 genes. Only two genes (N-methyl-D-aspartate (NMDA) receptor 2B and guanosine triphosphate (GTP)-binding protein G-alpha-i1) were similarly affected by both thermogenesis-inducing conditions, undergoing an increment of expression. RT-PCR and immunoblot evaluations confirmed the modulation of NMDA receptor 2B and GTP-binding protein G-alpha-i1, only. This corresponds to 0.93% of all the responsive genes and 0.17% of the analyzed genes. These results indicate that distinct environmental thermogenic stimuli can modulate predominantly distinct profiles of genes reinforcing the complexity and multiplicity of the hypothalamic mechanisms that regulate energy conservation and expenditure.

Deletion of Tumor Necrosis Factor-alpha Receptor 1 (TNFR1) Protects against Diet-induced Obesity by Means of Increased Thermogenesis

In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-alpha inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O(2) consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O(2) consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-alpha signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis.

Postprandial thermogenesis in Bothrops moojeni (Serpentes: Viperidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The thermogenesis of digestion in rattlesnakes

Some snakes have a feeding regime characterized by the infrequent ingestion of relatively large meals, causing impressive increments in post-prandial metabolism. Metabolism remains elevated for many days, while digestion proceeds, resulting in considerable investment of time and energy. Snakes actively adjust thermoregulatory behavior to raise their body temperature during digestion, exhibiting a post-prandial thermophilic response that accelerates digestion at the expense of higher metabolic rates. In the present study, we investigated the possibility that endogenously derived heat, originating as a byproduct of the post-prandial increase in metabolism, could itself contribute to the elevated body temperature during digestion in the South American rattlesnake Crotalus durissus. We assessed heat production, at a constant environmental temperature, by taking infrared (IR) images of snakes during fasting and after being fed meals varying from 10% to 50% of their own body masses. Our results show clearly that digesting rattlesnakes have significantly increased body temperatures, even when precluded from adjusting their thermoregulatory behavior. The feeding-derived thermogenesis caused the surface body temperature of rattlesnakes to increase by 0.9-1.2degreesC, a temperature change that will significantly affect digestive performance. The alterations in body temperature following feeding correlated closely with the temporal profile of changes in post-prandial metabolism. Moreover, the magnitude of the thermogenesis was greater for snakes fed large meals, as was the corresponding metabolic response. Since IR imaging only assesses surface temperatures,, the magnitude of the thermogenesis and the changes in deep core temperature could be even more pronounced than is reported here.