Brown adipose tissue specific lack of uncoupling protein 3 is associated with impaired cold tolerance and reduced transcript levels of metabolic genes

Uncoupling protein 3 (Ucp3) is located within the mitochondrial inner membrane of brown adipose tissue and skeletal muscle. It is thought to be implicated in lipid metabolism and defense against reactive oxygen species. We previously reported on a mutation in our breeding colony of Djungarian hamsters (Phodopus sungorus) that leads to brown adipose tissue specific lack of Ucp3 expression. In this study we compared wildtype with mutant hamsters on a broad genetic background. Hamsters lacking Ucp3 in brown adipose tissue displayed a reduced cold tolerance due to impaired nonshivering thermogenesis. This phenotype is associated with a global decrease in expression of metabolic genes but not of uncoupling protein 1. These data implicate that Ucp3 is necessary to sustain high metabolic rates in brown adipose tissue.     

Central and peripheral administration of amylin induces energy expenditure in anesthetized rats

Amylin is a peptide hormone that is co-released with insulin from pancreatic β-cells following a meal. Intracerebroventricular (icv) administration of amylin (1–100 pmol), or an amylin agonist, salmon calcitonin, elicited dose-dependent thermogenic, tachycardic, and hyperthermic responses in urethane-anesthetized rats. Intravenous (iv) administration of higher doses of amylin (100 pmol–20 nmol) also induced similar responses, although the amplitudes of these responses were significantly smaller than those elicited by icv administration, suggesting the primary action of amylin to be in the brain. However, the iv administration of amylin induced the responses slightly faster than the icv injection, the former responses occurring <4 min and the latter, at 8–10 min, after the administration. The iv but not the icv injection of amylin increased the respiratory exchange ratio transiently (<20 min), though the thermogenic response lasted for a longer period after both injections, indicating a shift from mixed fuel to predominantly carbohydrate utilization in the initial phase of thermogenesis induced by the iv injection of amylin. The differences in substrate utilization and latency of the responses suggest that the actions of amylin include partly different targets when administered centrally and peripherally. Moreover, pretreatment with a β-adrenergic blocker, propranolol (5 mg kg⁻¹, iv), blocked all responses elicited by either icv or iv administration of amylin, whereas ablation of the area postrema in the hindbrain did not influence the effects of icv-administered amylin. These results suggest the involvement of amylin in postprandial energy expenditure, mediated by peripheral β-adrenoceptors.     

Unstable, self-limiting thermochemical temperature oscillations in Macrozamia cycads

Field measurements and laboratory experiments on the Australian cycads Macrozamia lucida and Macrozamia macleayi demonstrate that their cones' diel peak thermogenic temperature increase varies systematically with cone stage, with single thermogenic temperature peaks occurring daily for up to 2 weeks and reaching 12 degrees C above ambient at midstage. The initiation, magnitude and timing of those peaks are strongly modulated by ambient temperature; the period between successive thermogenic temperature peaks is not circadian, and light is neither necessary nor sufficient to initiate a thermogenic event. A mathematical analysis is developed that provides a unified explanation of the experimental results. It describes these unstable, self-limiting thermogenic events in terms of conservation of energy and a first-order chemical reaction rate model that includes an Arrhenius equation dependence of the cone's metabolic heating rate on the cone temperature.     

Effects of Dinner Composition on Postprandial Macronutrient Oxidation in Prepubertal Girls

Objective: To see whether a fat‐rich (50%) evening meal promoted fat oxidation and a different spontaneous food intake on the following day at breakfast than a meal with a lower fat content (20%) in 10 prepubertal obese girls. Research Methods and Procedures: The postabsorptive and postprandial (10.5 hours) energy expenditure after a low‐fat (LF) (20% fat, 68% carbohydrate, 12% protein) and an isocaloric (2.1 MJ) and isoproteic high‐fat (HF; 50% fat, 38% carbohydrate, 12% protein) meal were measured by in direct calorimetry. Results: Fat oxidation was not significantly different after the two meals [LF, 31 ± 9 vs. HF, 35 ± 9 g/10.5 hours, p = not significant (NS)]. The girls oxidized 1.8 ± 0.9 times more fat than that ingested (11.1 grams) with the LF meal vs. 0.3 ± 0.3 times more fat than that ingested (27.1 grams) with the HF meal (p < 0.001). Carbohydrate oxidation was significantly higher after an LF than an HF meal (39 ± 12 vs. 29 ± 9 g/10.5 hours, p < 0, 05). At breakfast, the girls spontaneously ingested a similar amount of energy (1.5 ± 0.7 vs. 1.5 ± 0.6 MJ, p = NS) and macronutrient proportions (fat, 23% vs. 26%, p = NS; protein, 9% vs. 10%; carbohydrate, 68% vs. 64%,) independently of their having eaten an HF or an LF dinner. Discussion: An HF dinner did not stimulate fat oxidation, and no compensatory effect in spontaneous food intake was observed during breakfast the following morning. Cumulated total fat oxidation after dinner was higher than total fat ingested at dinner, but a much larger negative fat balance was observed after the LF meal. Spontaneous energy and nutrient intakes at breakfast were similar after LF and HF isocaloric, isoproteic dinners. This study points out the lack of sensitivity of short‐term fat balance to subsequently readjust fat intake and emphasizes the importance of an LF meal to avoid transient positive fat imbalance.     

Correlation between torpor frequency and capacity for non-shivering thermogenesis in the Siberian hamster (Phodopus sungorus)

We investigated the correlation between torpor frequency and capacity for non-shivering thermogenesis (NST) in Siberian hamsters (Phodopus sungorus) during 25 weeks of acclimation to cold and short days. We hypothesized that torpor use is conditioned on the development of brown adipose tissue (BAT) capacity for NST. We found that (1) the degree of noradrenaline (NA)-induced hyperthermia was positively correlated with torpor frequency and its length and depth, and (2) the maximum response to NA occurred at the time of day when hamsters naturally arouse from torpor. The present study quantifies the correlation between torpor frequency and NST capacity and we suggest that a well-developed NST capacity is a prerequisite for the occurrence of torpor.     

Sex‐Dependent Dietary Obesity,Induction of UCPs,and Leptin Expression in Rat Adipose Tissues

Objective: The aim of this study was to determine the sex‐dependent differences in the response of key parameters involved in thermogenesis and control of body weight in brown adipose tissue (BAT) and white adipose tissue (WAT) in postcafeteria‐fed rats, a model of dietary obesity. Research Methods and Procedures: BAT and WAT were obtained from male and female control and postcafeteria‐fed Wistar rats. Postcafeteria‐fed rats were initially fed with cafeteria diet from day 10 of life until day 110 (cafeteria period) and with standard chow diet from then until day 180 of life (postcafeteria period). Body mass and energy intake were evaluated. Biometric parameters were analyzed in interscapular BAT (IBAT). Levels of uncoupling protein 1 (UCP1), α₂‐adrenergic receptor (AR), and β₃‐AR proteins and UCP1, UCP2, UCP3, β₃‐AR, and leptin mRNAs, in IBAT or WAT, were studied by Western blot and Northern blot analyses, respectively. Results: Rats attained 59% (females) and 39% (males) increase in body weight at the end of the cafeteria period. During the postcafeteria period, the rats showed a loss of body weight, which was higher in females. Postcafeteria‐fed female rats also presented higher activation of thermogenic parameters in IBAT, including UCP1, UCP2, and UCP3 mRNAs. Female control rats showed lower levels of both α2 and β₃‐ARs in BAT compared with male rats, but these levels in postcafeteria‐fed female and male rats were the same, because males tended to down‐regulate them. Levels of leptin mRNA in response to the postcafeteria state depended on gender and the specific WAT depot studied. Discussion: It is suggested that in postcafeteria‐fed female rats, BAT thermogenic capacity becomes more efficiently activated than in males. Female rats also showed a bigger weight loss. The parallel regulation of the levels of UCP2 and UCP3 mRNAs, with respect to UCP1 mRNA, with higher activation in female postcafeteria‐fed rats, suggests a possible role of both UCP2 and UCP3 in the regulation of energy expenditure and in the control of body weight. The distinct responses to overweight of α2 and β₃‐ARs—which were sex dependent—and leptin mRNA—which depended on both sex and WAT depot—also support the different response of thermogenesis‐related parameters between overweight males and females.     

The Adipose Tissue Phenotype of Hormone‐Sensitive Lipase Deficiency in Mice

Objective: To directly ascertain the physiological roles in adipocytes of hormone‐sensitive lipase (HSL; E.C. 3.1.1.3), a multifunctional hydrolase that can mediate triacylglycerol cleavage in adipocytes. Research Methods and Procedures: We performed constitutive gene targeting of the mouse HSL gene (Lipe), subsequently studied the adipose tissue phenotype clinically and histologically, and measured lipolysis in isolated adipocytes. Results: Homozygous HSL^?/? mice have no detectable HSL peptide or cholesteryl esterase activity in adipose tissue, and heterozygous mice have intermediate levels with respect to wild‐type and deficient littermates. HSL‐deficient mice have normal body weight but reduced abdominal fat mass compared with normal littermates. Histologically, both white and brown adipose tissues in HSL^?/? mice show marked heterogeneity in cell size, with markedly enlarged adipocytes juxtaposed to cells of normal morphology. In isolated HSL^?/? adipocytes, lipolysis is not significantly increased by β₃‐adrenergic stimulation, but under basal conditions in the absence of added catecholamines, the lipolytic rate of isolated HSL^?/? adipocytes is at least as high as that of cells from normal controls. Cold tolerance during a 48‐hour period at 4 °C was similar in HSL^?/? mice and controls. Overnight fasting was well‐tolerated clinically by HSL^?/? mice, but after fasting, liver triglyceride content was significantly lower in HSL^?/? mice compared with wild‐type controls. Conclusions: In isolated fat cells, the lipolytic rate after β‐adrenergic stimulation is mainly dependent on HSL. However, the observation of a normal rate of lipolysis in unstimulated HSL^?/? adipocytes suggests that HSL‐independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in mice has a modest effect under normal fed conditions and is compatible with normal maintenance of core body temperature during cold stress. However, the lipolytic response to overnight fasting is subnormal.     

布氏田鼠冷暴露中褐色脂肪组织的增补及解偶联蛋白基因表达

布氏田鼠 (Microtusbrandti)随机分组暴露在冷环境 [12L∶12D ,(4± 2 )℃ ]中 12h ,1d ,3d ,7d ,14d ,2 1d和 2 8d ;对照组生活在温暖环境下 [12L∶12D ,(2 5± 2 )℃ ]。与对照组相比 ,布氏田鼠的褐色脂肪组织 (BAT)重量在冷暴露 12h～ 3d时降低 ,7～ 2 1d时则增加。 7～ 2 8d冷暴露组动物的BAT总蛋白和总DNA含量均比对照组明显提高。冷环境中的布氏田鼠解偶联蛋白 (UCP)的mRNA随时间的延长而表达上调 ,在冷暴露 2 1d时达到高峰。结果表明 ,冷暴露能够诱导布氏田鼠BAT细胞增补和UCP基因表达 ,从而使适应性产热增加。     

内蒙古库布齐沙地四种啮齿动物非颤拌性产热的季节变化

为了解非颤抖性产热在内陆荒漠小型哺乳动物适应性热能调节中的作用,1997年对库布齐荒漠沙地环境4种啮齿动物：三趾跳鼠（Dipus sagitta)、子午沙鼠（Meriones meridianus)、小毛足鼠（Phodopus roborovskii)和黑线仓鼠（Cricetulus barabensis)的非颤抖性产热季节变化进行了测定。4种动物的非颤抖性产热在秋季低温刺激下明显高于夏季,而且小毛足鼠和黑线仓鼠在秋季的最大非颤抖性产热分别高于春季14％和35％。典型荒漠种小毛足鼠的季节变化最明显,夏季最低。结果表明,生活在内陆干旱地区的动物生长期进化过程中,发展了良好的非颤抖性产热体温调节机制适应环境温度的季节变化。