Food-induced thermogenesis in obese children

In 11 obese children aged 12.5 (±0.7) years with normal glucose tolerance and 7 lean, control children aged 11.9±0.7 years the preload resting energy expenditure and thermogenic response to a standardised meal was measured by indirect calorimetry. Preload energy expenditure was higher in obese children when expressed in absolute terms than in controls, but was not different when corrected for lean body weight. Four children with obesity of recent onset had lower food-induced thermogenesis and insulin response then seven overweight children with long-standing obesity. Food-induced thermogenesis and insulin response showed a significant positive correlation.It is concluded that food-induced thermogenesis is reduced in the early phase of childhood obesity but increased in the later phase when hyperinsulinaemia develops, pointing towards an important role of insulin in food-induced thermogenesis.Abbreviations EE energy expenditure - LBW lean body weight - FIT food-induced thermogenesis - IRI immunoreactive insulin - GH growth hormone - FFA free fatty acids - LR low responder - HR high responder - RO respiratory quotient     

Peroxisome proliferator-activated receptor δ (PPARδ), a novel target site for drug discovery in metabolic syndrome

The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)α and γ agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARδ functions is lagging behind because specific PPARδ agonists have not been developed. The appearance of new PPARδ agonists is brightening the prospects for elucidating the physiological role of PPARδ. PPARδ is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARδ agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARδ agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARδ may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARδ agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARδ itself and its agonists in the future.     

Hyperthermic reactions induced by orexin A: role of the ventromedial hypothalamus

This experiment tested the involvement of the ventromedial hypothalamus (VMH) in the sympathetic and hyperthermic reactions induced by an intracerebroventricular (i.c.v.) injection of orexin A (1.5 nmol). In the first part of the experiment, the firing rate and cytochrome oxidase activity of the VMH neurons, and the colonic temperature were monitored in 12 urethane-anaesthetized rats before an i.c.v. injection of orexin and over a period of 2 h after the injection. Orexin induced an increase in the firing rate, colonic temperature and cytochrome oxidase activity. A group of 12 rats was used as a control: saline, but not orexin, was injected. No modifications in the firing rate, cytochrome oxidase reactivity and colonic temperature were noted. In the second part of the experiment, 12 rats were anaesthetized and lesioned bilaterally in the VMH with an injection of ibotenic acid. Sham lesions were carried out in 12 control rats. After 48 h, all animals were anaesthetized with ethyl-urethane. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored before and over a period of 2 h after an i.c.v. injection of orexin or saline in the lesioned and sham-lesioned rats. Orexin increased the sympathetic firing rate, IBAT and colonic temperatures and heart rate in the sham-lesioned rats. These increases were reduced by lesion of VMH. Saline did not induce any modification. These findings indicate that the VMH is involved in the control of the orexin-induced hyperthermia.     

Galanin-like peptide as a link between metabolism and reproduction

Galanin-like peptide (GALP) is a hypothalamic neuropeptide that binds and activates galanin receptors in vitro. Following the discovery of GALP, researchers have attempted to properly place it in the context of galanin receptor physiology. Central injections of GALP have revealed some common actions with galanin, such as acutely increased food intake and suppression of the thyroid axis. Other actions are unique to GALP, such as long-term inhibition of food intake and stimulation of luteinizing hormone (LH) secretion in male rats. GALP and galanin also produce differential effects on expression of the immediate early gene product Fos in the brain. Determining which of these actions are dependent on galanin receptors (versus a putative GALP-specific receptor), as well as which actions represent the authentic physiology of endogenous GALP will require continued experimentation. GALP gene expression is positively regulated by several hormones involved in the control of energy balance and metabolism, namely leptin, insulin and thyroid hormone. Based on current evidence, GALP neurones may serve as a hypothalamic relay, transmitting information from the periphery to circuits within the brain involved in the physiological control of metabolism and reproduction.     

Differential regulation of brown adipose and splanchnic sympathetic outflows in rat: roles of raphe and rostral ventrolateral medulla neurons

1. The medullary premotor neurons determining the sympathetic outflow regulating cardiac function and vasoconstriction are located in the rostral ventrolateral medulla (RVLM). The present study sought evidence for an alternative location for the sympathetic premotor neurons determining the sympathetic nerve activity (SNA) controlling brown adipose tissue (BAT) metabolism and thermogenesis. 2. The tonic discharge on sympathetic nerves is determined by the inputs to functionally specific sympathetic preganglionic neurons from supraspinal populations of premotor neurons. Under normothermic conditions, BAT SNA was nearly silent, while splanchnic (SPL) SNA, controlling mesenteric vasoconstriction, exhibited sustained large-amplitude bursts. 3. The rostral raphe pallidus (RPa) contains potential sympathetic premotor neurons that project to the region of sympathetic preganglionic neurons in the thoracic spinal cord. Disinhibition of neurons in RPa elicited a dramatic increase in BAT SNA, with only a small rise in SPL SNA. 4. Splanchnic SNA was strongly influenced by the baroreceptor reflex, as indicated by a high coherence with the arterial pressure wave, a significant amplitude modulation over the time-course of the cardiac cycle and a marked inhibition of SPL SNA during a sustained increase in arterial pressure. When activated, the bursts in BAT SNA exhibited no correlation with arterial pressure and were not affected by increases in arterial pressure. 5. Because these characteristics and reflex responses in sympathetic outflow have been shown to arise from the on-going or altered discharge of sympathetic premotor neurons, the marked differences between SPL and BAT SNA provide strong evidence supporting the hypothesis that vasoconstriction and thermogenesis (metabolism) are controlled by distinct populations of sympathetic premotor neurons, the former in the RVLM and the latter, potentially, in the RPa.     

The β3-Adrenergic System and β3-Adrenergic Agonists

Reviews in Endocrine and Metabolic Disorders -     

Reduced Postprandial Energy Expenditure in Women Predisposed to Type 2 Diabetes

Type 2 (non-insulin dependent) diabetes is so common that it has been hypothesized that in the course of evolution the predisposition to it may have conferred some advantage, before or during the reproductive years. It is frequently preceded by gestational diabetes. In order to test the basis for the hypothetical advantage, energy expenditure was investigated in 10 women with documented transient diabetes in a previous pregnancy. They were studied early in a subsequent pregnancy while glucose tolerance was still normal and 9 were re-studied after pregnancy. Their results were compared with normal matched controls. During pregnancy, resting energy expenditure was similar in the study group and controls (6.58 (5.77–7.55) median (range) vs 6.91 (6.56–7.36) MJ day^-1, respectively). However, the energy response to a mixed meal (42 kJ kg^-1 lean body mass) was decreased in the study group (45 (33–68) vs 76 (50–89) kJ, p<0.05). After pregnancy resting energy expenditure was again similar in the two groups, but the decrease in postprandial thermogenesis persisted (78 (59–84) vs 92 (79–105) kJ, p<0.05). The patients were resistant to exogenous insulin, 0.05 U kg^-1 intravenously (slope of the plasma glucose decline in the 15 min after insulin; during pregnancy patients 52 (37–92) vs controls 111 (104–121) μmol l^-1 min^-1, p<0.01; after pregnancy 130 (88–156) vs controls 186 (152–221) μmol l^-1 min^-1, p<0.01). The postprandial energy saving in these women could constitute an evolutionary advantage. Insulin resistance may be the mechanism for limiting postprandial thermogenesis.