Disease relevance of Thermogenesis

• Furthermore, we provide evidence that the role of Cidea in regulating thermogenesis, lipolysis and obesity may be mediated in part through its direct suppression of Ucp1 activity [1].
• Lep(ob/ob) mice were especially sensitive to i.c.v. and systemic ADP, which resulted in increased thermogenesis, weight loss and reduction in serum glucose and lipid levels [2].
• The latter is the preponderant determinant of the impaired adaptive thermogenesis and hypothermia in cold-exposed Dio2(-/-) mice [3].
• In humans caffeine stimulates thermogenesis by unknown mechanisms and its effect on body weight has not been studies [4].
• Obese individuals and obese patients with non-insulin-dependent diabetes mellitus commonly have a decrease in glucose-induced thermogenesis [5].

Psychiatry related information on Thermogenesis

• Consistent with the increased lean body mass of s/s animals, locomotor activity and acute cold tolerance (partly a measure of shivering thermogenesis) in s/s mice were modestly but significantly improved compared with db/db mice, although they were decreased compared with wild-type mice [6].
• These results suggest that higher levels of ghrelin are associated with low levels of resting and postprandial thermogenesis, which is independent of individual differences in fat-free mass and fat mass [7].
• Hypothalamic neuronal histamine modulates adaptive behavior and thermogenesis in response to endogenous pyrogen [8].
• Effects of 4-hydroxyamphetamine on in vivo brown adipose tissue thermogenesis and feeding behavior in the rat [9].
• Whilst there may be some causal relationship between increased corticosterone secretion, decreased plasma thyroid hormone levels and reduced metabolic heat production it is unlikely that these responses alone account for the adjustments in energy expenditure observed in short term food deprivation [10].

High impact information on Thermogenesis

• Facultative thermogenesis is activated by the SNS but is modulated by TH [11].
• Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves [12].
• The thermogenic activity of brown adipose tissue (BAT), important for adaptive thermogenesis and energy expenditure, is mediated by the mitochondrial uncoupling protein1 (Ucp1) that uncouples ATP generation and dissipates the energy as heat [1].
• TIF2-/- mice are protected against obesity and display enhanced adaptive thermogenesis, whereas SRC-1-/- mice are prone to obesity due to reduced energy expenditure [13].
• These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis [14].

Chemical compound and disease context of Thermogenesis

• Effects of sucrose vs starch diets on in vivo insulin action, thermogenesis, and obesity in rats [15].
• 2. Neither pretreatment with the ganglion blocker hexamethonium (20 mg kg(-1), I.P.) or the beta-adrenergic antagonist propranolol (10 mg kg(-1), I.P.), nor bilateral cervical vagotomy or bilateral adrenalectomy had any effect on the osmotically induced thermogenesis [16].
• O2*- generation in the mitochondrial respiratory chain and its cycling across the inner membrane may have the role of an endogenous protonophore in regulating and partitioning energy transduction and heat production, as well as in pathogenesis of mitochondrial diseases, aging, and apoptosis [17].
• Findings suggest that DHEA acetate treatment affected body weight, body composition and utilization of dietary energy by both impairing fat synthesis and promoting fat-free tissue deposition and resting heat production [18].
• Suppression of norepinephrine-induced thermogenesis in human obesity by diet and weight loss [19].

Biological context of Thermogenesis

• Hypothalamic neuropeptide Y stimulates food intake, decreases thermogenesis, and increases plasma insulin and corticosterone levels making it a potential target [20].
• These mice are cold intolerant because they have impaired peripheral vasoconstriction and are unable to induce thermogenesis in brown adipose tissue through uncoupling protein (UCP1) [21].
• Consistent with these observations, translation of the peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC1), a transcriptional co-activator implicated in mitochondrial biogenesis and adaptive thermogenesis, is increased in white adipose tissue of Eif4ebp1-/- mice [22].
• Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis [3].
• Mice devoid of all hormone-binding TRs [TR alpha 1(-/-)beta(-/-) (TR-ablated mice)] had slightly decreased body temperature and much decreased basal metabolic rate, were still able to markedly increase metabolic rate in the cold, but were cold intolerant due to inadequate total heat production at low temperatures [23].

Anatomical context of Thermogenesis

• There are several mechanisms by which homeothermic animals increase heat production, including shivering, sympathetic nervous system activation and stimulation of thyroid hormone secretion [24].
• Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane [25].
• Our data broaden the known functions of aldosterone and suggest a potential role for MR in adipocyte differentiation and regulation of thermogenesis [26].
• Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific [27].
• Neuropeptide Y administered intracerebroventricularly and into the paraventricular nucleus of the hypothalamus stimulates feeding and decreases brown adipose tissue thermogenesis [28].

Associations of Thermogenesis with chemical compounds

• Photoperiodic control and effects of melatonin on nonshivering thermogenesis and brown adipose tissue [29].
• Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) has been shown to regulate adaptive thermogenesis and glucose metabolism [30].
• The glucose-induced thermogenesis (GIT) was 6.5 +/- 0.3% before and 4.6 +/- 0.5% (P less than 0.02) after propranolol [31].
• Confirmation of the importance of fatty acid oxidation to thermogenesis came from our finding that mice carrying the targeted inactivation of the long chain acyl CoA dehydrogenase gene (Acadl) are also sensitive to the cold [32].
• Together with recent functional data, these results strongly suggest that dopaminergic D1 mechanisms--i.e., activation of adenylate cyclase and formation of cyclic AMP--may be involved in cold-induced, nonshivering, and/or diet-induced thermogenesis [33].

Gene context of Thermogenesis

• UCP1 induces heat production by uncoupling respiration from ATP synthesis [34].
• With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene [35].
• While UCP1 is known to play an important role in regulating heat production during cold exposure, the biological functions of UCP2 and UCP3 are unknown [36].
• In contrast, expression of genes associated with cholesterol metabolism (sterol-regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl-CoA reductase, acyl-CoA:cholesterol acyltransferase-1) and thermogenesis (uncoupling protein-2) was upregulated in both WAT and BAT of HSL-/- mice [37].
• Although core temperature was normal, surface temperature was increased in Dgat1(-/-) mice, most likely reflecting an active mechanism to dissipate heat from increased thermogenesis [38].

Analytical, diagnostic and therapeutic context of Thermogenesis

• Glucose-induced thermogenesis (GIT) after a 100-g oral glucose load was measured by continuous indirect calorimetry in 32 nondiabetic and diabetic obese subjects and compared to 17 young and 13 middle aged control subjects [39].
• Left ventricular heat production (PH,lv) was compared with myocardial O2 consumption (P met O2) and mechanical parameters in intact anaesthetized dogs before and after acute volume overload induced by a perfusion of LMW dextran [40].
• Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3-4% (p less than 0.02) over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects [41].
• Thus, we show equal availability of reduced and oxidized plasma ascorbate during metabolically demanding thermogenesis and reperfusion associated with arousal from hibernation [42].
• Glutamate microinjection (1 M, 250 nl) into the hypothalamic supraoptic nucleus (SON) stimulated heat production in brown adipose tissue (BAT) and caused a rapid and sustained increase in interscapular BAT and core temperatures in urethane-anaesthetized rats [43].

References