guanosine-diphosphate and Hyperphagia

To establish whether changes in skeletal muscle mitochondrial efficiency contribute to increased energy expenditure and decreased metabolic efficiency of overeating rats with increased thermogenesis, we measured basal proton leak, fatty acid-induced uncoupling and uncoupling protein 3 (UCP3) content in subsarcolemmal and intermyofibrillar skeletal muscle mitochondria. Intermyofibrillar, but not subsarcolemmal, mitochondria from rats with increased thermogenesis exhibited a lower proton leak compared with controls. In both mitochondrial populations from rats with increased thermogenesis, fatty acid-induced uncoupling was increased significantly and a small recoupling effect of GDP was detected. In addition, intermyofibrillar and subsarcolemmal mitochondria from rats with increased thermogenesis showed higher UCP3 contents than controls. These results point out that metabolic efficiency in subsarcolemmal and intermyofibrillar mitochondria from rats with increased thermogenesis is differently regulated. In fact, in intermyofibrillar mitochondria both basal proton leak and fatty acid-induced uncoupling are altered, while in subsarcolemmal mitochondria only fatty acid-induced uncoupling increases. Both mitochondrial populations in skeletal muscle cells from rats with increased thermogenesis display an increased fatty acid-induced uncoupling and UCP3 content, which could contribute to avoiding obesity.

Topics: Animals; Carrier Proteins; Dietary Fats; Energy Metabolism; Fatty Acids; Guanosine Diphosphate; Hyperphagia; Ion Channels; Male; Mitochondria, Muscle; Mitochondrial Proteins; Muscle, Skeletal; Myofibrils; Protons; Rats; Rats, Wistar; Sarcolemma; Thermogenesis; Uncoupling Agents; Uncoupling Protein 3

We investigated the relative importance of overeating, thermogenesis, and uncoupling protein (UCP) expression in determining the severity of obesity in male Wistar rats fed a highly palatable diet. After 2 wk of feeding, body weight did not differ significantly from controls (248 +/- 4 vs. 229 +/- 3 g; P > 0.3), but rectal temperature, brown adipose tissue (BAT) mass, UCP3 expression in gastrocnemius muscle, and UCP2 expression in white adipose tissue (WAT) were all elevated in diet-fed animals. In a further study, rats fed a palatable diet for 8 wk exhibited higher energy intake and rectal temperature than controls. Dietary-obese rats were divided into high (427-490 g; n = 8) and low (313-410 g; n = 10) weight gainers. The high gainers ate significantly more than the low gainers, and energy intake was positively correlated with weight gain (r(2) = 0.72, P < 0.01). UCP2 and UCP3 mRNA levels in gastrocnemius muscle were significantly increased above lean controls in all diet-fed animals, whereas UCPs in WAT and BAT did not differ significantly from controls. Whereas rats fed palatable food exhibited a thermogenic response, there was no significant difference in core temperature between high and low gain groups (37. 5 +/- 0.1 vs. 37.6 +/- 0.1 degrees C; P > 0.5). We conclude that a higher energy intake is the critical factor determining susceptibility to dietary obesity in unselected Wistar rats.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Temperature; Body Weight; Carrier Proteins; Diet; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Guanosine Diphosphate; Hyperphagia; Insulin; Ion Channels; Leptin; Male; Membrane Proteins; Membrane Transport Proteins; Mitochondria; Mitochondrial Proteins; Muscle, Skeletal; Obesity; Protein Biosynthesis; Rats; Rats, Wistar; Triglycerides; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3

Resting oxygen consumption was elevated by 30% in young rats fed a cafeteria diet compared with their chow-fed controls and by 22% in cafeteria-fed, adrenalectomized (ADX) rats compared with the ADX chow-fed group, but injection of propranolol reduced oxygen consumption in the cafeteria-fed animals and abolished these differences. Brown adipose tissue (BAT) mass was increased by cafeteria feeding, and the activity of the mitochondrial proton conductance pathway (assessed from purine nucleotide binding) was enhanced by adrenalectomy and by cafeteria feeding. Norepinephrine turnover in BAT (determined from the time-dependent loss of tissue [3H]norepinephrine specific activity) was increased by 105% in sham-operated, cafeteria-fed rats, by 142% in chow-fed ADX rats, and by 400% in cafeteria-fed ADX rats, compared with chow-fed controls. Cardiac norepinephrine turnover was elevated by 80% in sham-operated, cafeteria-fed rats, but unaffected by adrenalectomy. These data indicate that the enhanced thermogenesis and BAT activity induced by adrenalectomy in chow- or cafeteria-fed rats is due to increased sympathetic activity in the tissue.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Basal Metabolism; Body Temperature Regulation; Feeding and Eating Disorders; Guanosine Diphosphate; Hyperphagia; Male; Myocardium; Norepinephrine; Oxygen Consumption; Rats; Rats, Inbred Strains; Sympathetic Nervous System

Measurements of energy balance, thermogenic responses to noradrenaline and brown adipose tissue (BAT) activity were performed in male Lister-hooded rats aged 3.5 and 6.5 months, and fed either a pelleted control diet or a palatable cafeteria diet for 15 d. Cafeteria feeding produced increases in energy intake of 34 and 30 per cent in 3.5 and 6.5-month-old rats respectively, and energy expenditure was elevated by 25 and 10 per cent in these groups. Three-and-a-half-month-old cafeteria-fed rats gained more energy than their controls, but net energetic efficiency was significantly reduced, while in the older cafeteria rats, body energy gain was markedly increased without any apparent effect on net efficiency. The thermogenic response to noradrenaline was enhanced by cafeteria feeding at both ages. The younger cafeteria-fed rats showed significant increases in the mass, protein content and mitochondrial yield of BAT, and the activity of the mitochondrial proton conductance pathway, assessed from GDP-binding, was greater than their controls. The 6.5-month-old cafeteria group also showed hypertrophy of BAT and small, but not significant, increases in the protein content of the tissue and mitochondrial GDP-binding. These results demonstrate that rats aged 3.5 months can exhibit diet-induced thermogenesis and activate BAT in response to overfeeding, but the capacity for thermogenesis declines with age and was virtually absent in 6.5-month-old rats.

Topics: Adipose Tissue, Brown; Aging; Animals; Body Temperature Regulation; Energy Metabolism; Guanosine Diphosphate; Humans; Hyperphagia; Male; Mitochondria; Norepinephrine; Rats; Rats, Inbred Strains

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Diet; Energy Metabolism; Guanosine Diphosphate; Humans; Hyperphagia; Norepinephrine; Rats; Sodium-Potassium-Exchanging ATPase; Sympathetic Nervous System