Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPARgamma activation. Administration of the PPARgamma agonist rosiglitazone (15 mg/kg.d) for 7 d to male Sprague Dawley rats increased food intake (10%), feed efficiency (31%), weight gain (45%), spontaneous motor activity (60%), and BAT and WAT mass and reduced whole-body oxygen consumption. Consistent with an anabolic setting, rosiglitazone markedly reduced sympathetic activity to BAT and WAT (>50%) and thyroid status as evidenced by reduced levels of plasma thyroid hormones (T(4) and T(3)) and mRNA levels of BAT and liver T(3)-generating enzymes iodothyronine type 2 (-40%) and type 1 (-32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of the thyroid hormone receptor (THR) isoforms alpha1 (-34%) and beta (-66%) in BAT and isoforms alpha1 (-20%) and alpha2 (-47%) in retroperitoneal WAT. These metabolic effects were associated with a reduction in mRNA levels of the pro-energy expenditure peptides CRH and CART in specific hypothalamic nuclei. A direct central action of rosiglitazone is, however, unlikely based on its low brain uptake and lack of metabolic effects of intracerebroventricular administration. In conclusion, a reduction in BAT sympathetic activity and thyroid status appears to, at least partly, explain the PPARgamma-induced reduction in energy expenditure and the fact that up-regulation of thermogenic gene expression does not translate into functional stimulation of whole-body thermogenesis in vivo.

Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation.

Melanocortins are implicated in the control of energy intake/expenditure. Centrally administered melanotan II (MTII), a synthetic melanocortin 3/4-receptor agonist, decreases adiposity beyond that accountable by food intake decreases. Melanocortin-4 receptor (MC4-R) mRNA is expressed on sympathetic nervous system (SNS) outflow neurons to white adipose tissue (WAT) in Siberian hamsters, suggesting a role in lipid mobilization. Therefore, we tested whether third ventricular injections of MTII increased sympathetic drive to WAT and interscapular brown adipose tissue (IBAT) using norepinephrine turnover (NETO) as a measure of sympathetic drive. We also tested for MTII-induced changes in lipolysis-related WAT gene expression (beta3-adrenoceptors, hormone sensitive lipase) and IBAT thermogenesis (beta3-adrenoceptor, uncoupling protein-1). Finally, we tested whether third ventricularly injected MTII, a highly selective MC4-R agonist (cyclo[beta-Ala-His-D-Phe-Arg-Trp-Glu]NH2) increased or agouti-related protein decreased IBAT temperature in hamsters implanted with sc IBAT temperature transponders. Centrally administered MTII provoked differential sympathetic drives to WAT and IBAT (increased inguinal WAT, dorsosubcutaneous WAT and IBAT NETO, but not epididymal WAT and retroperitoneal WAT NETO). MTII also increased circulating concentrations of the lipolytic products free fatty acids and glycerol but not plasma catecholamines, suggesting lipid mobilization via WAT SNS innervation and not via adrenal medullary catecholamines. WAT or IBAT gene expression was largely unaffected by acute MTII treatment, but IBAT temperature was increased by MTII and the MC4-R agonist and decreased by agouti-related protein. Collectively, this is the first demonstration of central melanocortin agonist stimulation of WAT lipolysis through the SNS and confirms melanocortin-induced changes in BAT thermogenesis.

Supplementation of cow milk naturally enriched in polyunsaturated fatty acids and polyphenols to growing rats.

This study investigated whether intake of cow milk, naturally enriched with polyunsaturated fatty acids (PUFA, omega-3) and polyphenols (from propolis extract and vitamin E), from manipulation of cow's diet, would result in positive metabolic effects in rats from weaning until adulthood. Male Wistar rats were fed a standard chow diet or a hypercaloric diet (metabolically disturbed rats, obese) which was supplemented with either whole common milk, milk enriched with PUFA (PUFA-M) or milk enriched with PUFA and polyphenols (PUFA/P-M), at 5mL/kg body weight,having water as control. Whole milk supplementation increased initial weight gain and reduced gain in the adulthood of rats. Intake of common milk reduced cholesterol levels in non-obese rats and reduced insulin resistance in obese rats. PUFA-milk showed a decreasing effect on plasma triacylglycerol and VLDL concentrations, increasing plasma HDL concentration and reducing adipocyte size of non-obese rats, but no effect was observed in obese rats. PUFA/P-milk in obese rats resulted in greater deposition of muscle mass and mesenteric fat, with a tendency to lower LDL levels, and resulted a visceral fat accumulation in non-obese rats. Thus, whole common milk and PUFA-rich milk have shown to be beneficial in a normal metabolic condition, whereas common milk and milk enriched with PUFA and polyphenols improve metabolic effects of obesity.

Immediate and residual effects of low-dose nandrolone decanoate and treadmill training on adipose and reproductive tissues of male Wistar rats.

CONTEXT: Residual effects after nandrolone decanoate (ND) treatment are not reported. OBJECTIVE: Immediate and residual effects of low-dose ND and treadmill training were investigated. MATERIALS AND METHODS: Male rats were trained and/or ND-treated for four weeks and the assessments were made after this period or four weeks later. RESULTS: The groups did not differ in final plasma glucose or AUC of the ivGTT, but hyperinsulinemia was noticed in some trained/treated groups. Training with ND increased muscle mass and ND decreased the reproductive structures. Decreased fat with training was reversed by detraining. DISCUSSION: The anabolic action of ND on skeletal muscle was enhanced by training. Fat and lipid changes were more linked to training/detraining, but the effects of ND on the reproductive structures persisted after treatment. CONCLUSIONS: The effects of training on fat and muscle were not maintained after detraining, but low-dose ND had persistent effects on the reproductive structures.

Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation.

Surplus energy is principally stored in white adipose tissue (WAT) as triacylglycerol and mobilized via lipolysis through norepinephrine (NE) released from sympathetic nervous system terminals innervating WAT. We demonstrated that central melanocortin receptor agonism provokes differential sympathetic drives across WAT pads and interscapular brown adipose tissue (IBAT). Here we tested for differential WAT and IBAT sympathetic drive to known lipolytic stimuli {glucoprivation [2-deoxy-D-glucose (2-DG)], cold exposure (5 degrees C), food deprivation (16 h), or both cold exposure and food deprivation} by measuring NE turnover (NETO). Only inguinal WAT NETO significantly increased across all stimuli. Dorsal subcutaneous WAT NETO only increased with glucoprivation. Retroperitoneal WAT NETO increased with glucoprivation, cold and cold + food deprivation, but not by food deprivation. Epididymal WAT NETO was unaffected by glucoprivation but increased with cold, cold + food deprivation or food deprivation, but to a small significant degree. IBAT NETO was unaffected by glucoprivation or food deprivation, but increased with cold and cold + food deprivation. Plasma glucose decreased with food deprivation and increased with 2-DG administration or cold exposure. Plasma glycerol was increased with food deprivation, cold, and their combination but not with 2-DG, whereas plasma free fatty acids increased with food deprivation, cold + food deprivation, and 2-DG. These data show differential sympathetic drive to WAT and BAT for four different lipolytic stimuli, exemplifying the fat pad-specific pattern of WAT sympathetic drive across lipid-mobilizing conditions and emphasizing the need to analyze multiple adipose depots for measures of NETO and likely most measures.

Energetic responses to cold temperatures in rats lacking forebrain-caudal brain stem connections.

Hypothalamic neurons are regarded as essential for integrating thermal afferent information from skin and core and issuing commands to autonomic and behavioral effectors that maintain core temperature (T(c)) during cold exposure and for the control of energy expenditure more generally. Caudal brain stem neurons are necessary elements of the hypothalamic effector pathway and also are directly driven by skin and brain cooling. To assess whether caudal brain stem processing of thermal afferent signals is sufficient to drive endemic effectors for thermogenesis, heart rate (HR), T(c), and activity responses of chronic decerebrate (CD) and control rats adapted to 23 degrees C were compared during cold exposure (4, 8, or 12 degrees C) for 6 h. Other CDs and controls were exposed to 4 or 23 degrees C for 2 h, and tissues were processed for norepinephrine turnover (NETO), a neurochemical measure of sympathetic drive. Controls maintained T(c) for all temperatures. CDs maintained T(c) for the 8 and 12 degrees C exposures, but T(c) declined 2 degrees C during the 4 degrees C exposure. Cold exposure elevated HR in CDs and controls alike. Tachycardia magnitude correlated with decreases in environmental temperature for controls, but not CDs. Cold increased NETO in brown adipose tissue, heart, and some white adipose tissue pads in CDs and controls compared with their respective room temperature controls. These data demonstrate that, in neural isolation from the hypothalamus, cold exposure drives caudal brain stem neuronal activity and engages local effectors that trigger sympathetic energetic and cardiac responses that are comparable in many, but not in all, respects to those seen in neurologically intact rats.