Adaptive nonshivering thermogenesis may have profound effects on energy balance and is therefore therefore is a potential mechanism for counteracting the development of obesity. The molecular basis for adaptive nonshivering thermogenesis has remained a challenge that sparked acute interest with the identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to the original uncoupling protein-1 (UCP1), which is localized only in brown adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive nonshivering thermogenesis could be recruited by acclimation to cold. Remarkably, by successive acclimation, the UCP1-ablated mice could be made to subsist for several weeks at 4C during which they had to constantly produce heat at four times their resting levels. Despite these extreme requirements for adaptive nonshivering thermogenesis, however, no substitution of shivering by any adaptive nonshivering thermogenic process occurred. Thus, although the existence of, for example, muscular mechanisms for adaptive nonshivering thermogenesis has recurrently been implied, we did not find any indication of such thermogenesis. Not even during prolonged and enhanced demand for extra heat production was any endogenous hormone or neurotransmitter able to recruit any UCP1-independent adaptive nonshivering thermogenic process in muscle or in any other organ, and no proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to mediate adaptive nonshivering thermogenesis in the cold.

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Peroxisome proliferator-activated receptor ␥ coactivator 1␣ (PGC-1␣) is an attractive candidate gene for type 2 diabetes, as genes of the oxidative phosphorylation (OXPHOS) pathway are coordinatively downregulated by reduced expression of PGC-1␣ in skeletal muscle and adipose tissue of patients with type 2 diabetes. Here we demonstrate that transgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N 1 -acetyltransferase (SSAT) had reduced white adipose tissue (WAT) mass, high basal metabolic rate, improved glucose tolerance, high insulin sensitivity, and enhanced expression of the OXPHOS genes, coordinated by increased levels of PGC-1␣ and 5-AMP-activated protein kinase (AMPK) in WAT. As accelerated polyamine flux caused by SSAT overexpression depleted the ATP pool in adipocytes of SSAT mice and N 1 ,N 11 -diethylnorspermine-treated wild-type fetal fibroblasts, we propose that low ATP levels lead to the induction of AMPK, which in turn activates PGC-1␣ in WAT of SSAT mice. Our hypothesis is supported by the finding that the phenotype of SSAT mice was reversed when the accelerated polyamine flux was reduced by the inhibition of polyamine biosynthesis in WAT. The involvement of polyamine catabolism in the regulation of energy and glucose metabolism may offer a novel target for drug development for obesity and type 2 diabetes.Type 2 diabetes is a growing epidemic worldwide. Defects in insulin secretion and insulin action are fundamental disorders of this disease (30). Several mechanisms regulating insulin secretion and insulin action have been identified, but none of them is likely to explain completely the risk of type 2 diabetes. Previous studies have revealed novel mechanisms, distinct from the insulin signaling pathway, for type 2 diabetes. Mootha et al. (36) identified a set of genes involved in oxidative phosphorylation (OXPHOS), the expression of which was coordinately decreased in human diabetic muscle. Similarly, Patti et al. (40) found the downregulation of OXPHOS not only in individuals with type 2 diabetes but also in their first-degree relatives. In both of these studies, decreased peroxisome proliferator-activated receptor (PPAR) ␥ coactivator 1␣ (PGC-1␣) expression was responsible for the downregulation of OX PHOS genes. In addition, the expression of PGC-1␣ has been shown to be downregulated in white adipose tissue (WAT) of insulin-resistant (15) and morbidly obese (50) subjects.PGC-1␣ was first identified as a coactivator of PPAR␥ (45), and it plays a critical role in the regulation of adaptive thermogenesis. Subsequent studies have demonstrated that PGC-1␣ regulates mitochondrial biogenesis (49), uncoupling (45, 56), fatty acid oxidation (61), OXPHOS (36), glucose transport in muscle (35), hepatic gluconeogenesis (64), and skeletal muscle fiber-type switching (44). PGC-1␣ is highly expressed in brown adipose tissue (BAT), heart, and skeletal muscle and moderately expressed in liver, but a low expression level is found in WAT. The expression of PGC-1␣ is ind...

Summary 1.Basal metabolic rate (BMR) is the most widely used standard measurement of the cost of living. Despite the acknowledged phenotypic flexibility of BMR, little is known about the patterns of variation in wild animal populations. 2. We studied the sources of variation in BMR of great tit Parus major (L.) among individuals from two wild populations: Oulu (northern Finland) and Lund (southern Sweden) during six consecutive years. 3. By means of a multivariate approach, we found year, locality, date, previous week average minimum temperature, age, body mass, and the interaction between locality and year were the factors retained in the final model, together explaining 71·1% of the total variation in BMR. 4. Birds from Oulu ( n = 168) had a higher BMR than Lund birds ( n = 156), and their BMR varied more between years than that of Lund birds. The two populations reacted in the same way to the other sources of variation examined. 5. Great tits from both populations showed a positive relationship between BMR and body mass and a negative relationship between BMR and date, previous week average minimum temperature and age. 6. This study highlights the need to standardize BMR measurements when testing predictions about metabolic rates from individuals of wild populations.

Summary 1.We studied the resting metabolic rate (MR) from two great tit Parus major (Linnaeus) populations living in different winter regimes. Birds from the two different localities were exposed individually to +25 °C, 0 °C and −10 °C for the night in three consecutive sessions in random order. 2. Birds from Lund (Sweden) had a lower basal MR, as measured at thermoneutrality (+25 °C), than had birds from Oulu (Finland). Nevertheless, below thermoneutrality, birds from Oulu spent relatively more energy, especially at −10 °C. 3. Although the energy needed for thermoregulation decreased with increasing basal MR this relation is at a higher metabolic cost for birds in Oulu than for birds in Lund. 4. The higher basal MR in Oulu is probably a consequence of a higher maximal MR needed in the severe cold. Further, the observed MRs below thermoneutrality are lower than expected from published data. This suggests that all birds were probably hypothermic at −10 °C, particularly Lund birds, and that the use of controlled hypothermia in great tits may be more common than thought previously. Great tits seem to rely primarily on metabolic adjustment to cope with the harsh climatic conditions in the northernmost parts of its distribution.

USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet-induced dyslipidemia, obesity, insulin resistance, hepatic steatosis, and atherosclerosis. The favorable plasma lipid profile, including increased high-density lipoprotein cholesterol and decreased triglycerides, was coupled with increased energy expenditure due to activation of brown adipose tissue (BAT). Usf1 inactivation directs triglycerides from the circulation to BAT for combustion via a lipoprotein lipase-dependent mechanism, thus enhancing plasma triglyceride clearance. Mice lacking Usf1 displayed increased BAT-facilitated, diet-induced thermogenesis with up-regulation of mitochondrial respiratory chain complexes, as well as increased BAT activity even at thermoneutrality and after BAT sympathectomy. A direct effect of USF1 on BAT activation was demonstrated by an amplified adrenergic response in brown adipocytes after Usf1 silencing, and by augmented norepinephrine-induced thermogenesis in mice lacking Usf1. In humans, individuals carrying SNP (single-nucleotide polymorphism) alleles that reduced USF1 mRNA expression also displayed a beneficial cardiometabolic profile, featuring improved insulin sensitivity, a favorable lipid profile, and reduced atherosclerosis. Our findings identify a new molecular link between lipid metabolism and energy expenditure, and point to the potential of USF1 as a therapeutic target for cardiometabolic disease.

BackgroundThe plumage of birds is important for flying, insulation and social communication. Contour feathers cover most of the avian body and among other functions they provide a critical insulation layer against heat loss. Feather structure and composition are known to vary among individuals, which in turn determines variation in the insulation properties of the feather. However, the extent and the proximate mechanisms underlying this variation remain unexplored.Methodology/Principal FindingsWe analyzed contour feather structure from two different great tit populations adapted to different winter regimes, one northern population in Oulu (Finland) and one southern population in Lund (Sweden). Great tits from the two populations differed significantly in feather structure. Birds from the northern population had a denser plumage but consisting of shorter feathers with a smaller proportion containing plumulaceous barbs, compared with conspecifics from the southern population. However, differences disappeared when birds originating from the two populations were raised and moulted in identical conditions in a common-garden experiment located in Oulu, under ad libitum nutritional conditions. All birds raised in the aviaries, including adult foster parents moulting in the same captive conditions, developed a similar feather structure. These feathers were different from that of wild birds in Oulu but similar to wild birds in Lund, the latter moulting in more benign conditions than those of Oulu.Conclusions/SignificanceWild populations exposed to different conditions develop contour feather differences either due to plastic responses or constraints. Environmental conditions, such as nutrient availability during feather growth play a crucial role in determining such differences in plumage structure among populations.

Abstract. Sedentary passerine birds living in temperate and boreal regions need a high metabolic capacity for thermogenesis to survive winter conditions. As a consequence of the increased thermogenic capacity, basal energetic demands rise at a time when resources and time to acquire them decrease. In a previous study, great tits (Parus major) from two localities in Fennoscandia with contrasting winter conditions differed in their metabolic response to ambient temperature. To investigate the physiological basis underlying interpopulation differences we performed a commongarden experiment to test whether these differences were genetically based. We found basal metabolic rate to be higher in birds originating from transferred eggs from the southern population compared to the ones from the northern population, contrary to the relationship among birds living in their region of origin. Despite previous evidence suggesting that gene flow prevents local adaptation at the northern range limits of a species expanding northward, we found that great tits differ in their reaction norm to winter conditions according to the population of origin.