To assess BAT activity in humans at a population level, infrared thermography (IRT) represents a safe, readily repeatable and affordable alternative to 18F-FDG-PET. Building upon a previously proposed method by our laboratory, we further refined the image computational algorithm to quantify BAT activation in the cervical-supraclavicular (C-SCV) region of healthy young men under thermo-neutral and cold exposure conditions. Additionally, we validated the whole-body calorimeter (WBC) in reliably measuring cold-induced thermogenesis. The temperature gradient between C-SCV-deltoid regions, and the corresponding difference in heat power output, increased upon cold air exposure relative to thermo-neutral conditions (by 74.88 %, p<0.0001; and by 71.34 %, p<0.0001 respectively). Resting and cumulative energy expenditure (EE) rose significantly (by 13.14 % and 9.12 % respectively, p=0.0001) while positive correlations between IRT measures and EE were found with cold air exposure (percentage change in heat power gradient between ROI and deltoid, cold air: r2 =0.29, p=0.026, Pearson's correlation). IRT and WBC can be used to study BAT activation. The refined algorithm allows for more automation and objectivity in IRT data analysis, especially under cold air exposures.
Repeated exposure of newborn rats to a short-term cold load between day 10 and 30 after birth stimulates the physiological growth rate of the brown adipose tissue. This indicates that in the neonatal period the brown adipose tissue has no reserve thermogenic capacity to compensate an additional cold load and therefore the rate of tissue growth must be activated.
Cold exposure of rats leads to ameliorated glucose and triglyceride utilization with fema les displaying better adaptation to a cold environment. In the current study, we used hairless rats as a model of increased thermo genesis and analyzed gender- related effects on parameters of lipid and glucose metabolism in the spontaneously hypertensive (SHR) rats. Specifically, we compared hairless coisogenic SHR- Dsg4 males and females harboring mutant Dsg4 (desmoglein 4) gene versus their SHR wild type controls. Two way ANOVA showed significant Dsg4 genotype (hairless or wild type) x gender interaction effects on palmitate oxidation in brown adipose tissue (BAT), glucose incorporation into BAT determined by microPET, and glucose oxidation in skeletal muscles. In addition, we observed significant interaction effects on sensitivity of muscle tissue to insulin action when Dsg4 genotype affected these metabolic traits in males, but had little or no effects in females. Both wild type and hairless females and hairless males showed increased glucose incorporation and palmitate oxid ation in BAT and higher tissue insulin sensitivity when compared to wild type males. These findings provide evidence for gender-related differences in metabolic adaptation required for increased thermogenesis. They are consistent with the hypothesis that increased glucose and palmitate utilization in BAT and muscle is associated with higher sensitivity of adipose and muscle tissues to insulin action, J. Trnovská, J. Šilhavý, V. Zídek, M. Šimáková, P. Mlejnek, V. Landa, S. Eigner, K. Eigner Henke, V. Škop, O. Oliyarnyk, L. Kazdová, T. Mráček, J. Houštěk, M. Pravenec., and Obsahuje bibliografii
This experiment tested the effects of an intracerebroventricular injection of prostaglandin E1 on the sympathetic activation and the thermogenic changes in rats with ibotenate lesions of the ventromedial hypothalamus. Under pentobarbital anesthesia, twelve Sprague-Dawley male rats were lesioned bilaterally in the ventromedial hypothalamus with an injection of ibotenic acid (30 nmol into each side). Sham lesions were carried out in other twelve control rats. After 48 h, all animals were anesthetized with ethyl-urethane. The firing rate of the sympathetic nerves innervating the interscapular brown adipose tissue and the colonic and interscapular brown adipose tissue temperatures were monitored before and after an intracerebroventricular injection of prostaglandin E1 (500 ng) or saline. Prostaglandin E1 induced an increase in the firing rate of sympathetic nerves and the colonic and interscapular brown adipose tissue temperatures. These effects were reduced by the ventromedial hypothalamic lesion. Since ibotenic acid destroys cell bodies, the findings indicate that neurons of the ventromedial hypothalamus play a considerable role in the control of sympathetic activation and the thermogenic changes during prostaglandin E1 hyperthermia., M. Monda, A. Sullo, V. De Luca, A. Viggiano., and Obsahuje bibliografii
The effect of exogenous noradrenaline (NA) (1.6 mg.kg-1 i.p., 35 min prior sacrifice) on the activity of antioxidant enzymes (AOE) copper zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as lipid peroxides (LP) concentration were studied in the rat interscapular brown adipose tissue (IBAT) and heart of saline (controls) and Nω-nitro-L-arginine methyl ester (L-NAME) treated rats (10 mg.kg-1, i.p., during 3 days and 20 min before NA). NA differently affects both AOE activities and LP production in the IBAT and heart. Thus, NA inhibited the activity of all IBAT AOE and LP production while in the heart it markedly increased CAT activity only, but had no effect on any of SODs activities and LP concentration. L-NAME, a nitric oxide synthase blocker, completely abolished the NA-induced inhibition of the IBAT AOE and LP production, whereas in the heart it was without effect. In conclusion, these results indicate that both NA and L-NAME effects on AOE activity and LP production are tissue specific and also suggest that nitric oxide mediates the NA-induced inhibition of AOE activity and LP production in the IBAT only., A. Perovic, T. Vuckovic, G. Cvijic, J. Djordjevic, V. Davidovic., and Obsahuje bibliografii a bibliografické odkazy
Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Identification of genes responsible for BAT function would shed light on underlying pathophysiological mechanisms of metabolic disturbances. Recent linkage analysis in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), identified two closely linked quantitative trait loci (QTL) associated with glucose oxidation and glucose incorporation into BAT lipids in the vicinity of Wars2 (tryptophanyl tRNA synthetase 2 (mitochondrial)) gene on chromosome 2. The SHR harbors L53F WARS2 protein variant that was associated with reduced angiogenesis and Wars2 thus represents a prominent positional candidate gene. In the current study, we validated this candidate as a quantitative trait gene (QTG) using transgenic rescue experiment. SHR-Wars2 transgenic rats with wild type Wars2 gene when compared to SHR, showed more efficient
mitochondrial proteosynthesis and increased mitochondrial respiration, which was associated with increased glucose oxidation and incorporation into BAT lipids, and with reduced weight of visceral fat. Correlation analyses in RI strains showed that increased activity of BAT was associated with amelioration of insulin resistance in muscle and white adipose tissue. In summary, these results demonstrate important role of Wars2 gene in regulating BAT function and consequently lipid and glucose metabolism.
In as early as 1997, the World Health Organization officially recognized obesity as a chronic disease. The current epidemic of obesity and overweightness has aroused great interest in the study of adipose tissue formation. The transcription factor peroxisome proliferator-activated receptor γ (PPARγ) binds to the target gene promoter regulatory sequences, acting as a key factor in regulating the differentiation of preadipocytes in the adipose tissue, and plays an important role in regulating the adipocyte metabolism. A further understanding of the structure and expression characteristics of PPARγ, in addition to its mechanisms of action in adipocyte differentiation, may be applied to control obesity and prevent obesity-related diseases. In this article, recent studies investigating the effect of regulating PPARγ on adipocyte differentiation are reviewed. In particular, the structural characteristics, expression patterns, and molecular mechanisms of PPARγ function in adipocyte differentiation are considered., Hui Wu, Xiaohua Li, Chunyan Shen., and Obsahuje bibliografii
The activity of antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as that of the mitochondrial FAD-dependent a-glycerophosphate dehydrogenase (a-GPD) in the rat interscapular brown adipose tissue (IBAT) were studied after the treatment with methimazole (MMI) for three weeks or with iopanoic acid (IOP) for five days. Besides, the mitochondrial concentration of uncoupling protein-1 (UCP-1) and the activity of catecholamine degrading enzyme monoamine oxidase (MAO) in the IBAT as well as the activity of the catecholamine synthesizing enzyme, dopamine b-hydroxylase (DBH) in rat serum were examined. Judging by the significantly enhanced level of serum DBH, which is an index of sympathetic activity, and that of IBAT MAO, the increase in MnSOD and CAT activities in the IBAT of hypothyroid (MMI-treated) rats seems to be due to elevated activity of sympathetic nervous system (SNS). However, CuZnSOD activity is not affected by SNS. On the contrary, IOP, which is a potent inhibitor of T4 deiodination into T3 producing "local" hypothyroidism, did not change either SNS activity or activities of IBAT antioxidant enzyme. However, both treatments significantly decreased IBAT UCP-1 content and a-GPD activity suggesting that the optimal T3 concentration in the IBAT is necessary for maintaining basal levels of these key mitochondrial parameters., N. Petrović, G. Cvijić V. Davidović., and Obsahuje bibliografii