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PubMed2003

Prolactin, prolactin receptor and uncoupling proteins during fetal and neonatal development.

Uncoupling proteins (UCP) 1 and 2 are members of the subfamily of inner mitochondrial membrane carriers. UCP1 is specific to brown adipose tissue (BAT), where it is responsible for the rapid production of heat at birth. In fetal sheep UCP1 is first detectable at approximately 90 d of gestation; its abundance increases with gestational age and peaks at the time of birth. The mRNA and protein for both the long and short form of the prolactin (PRL) receptor (PRLR) are also highly abundant in BAT. Enhanced PRLR abundance in late gestation is associated with an increase in the abundance of UCP1. This relationship between PRLR and UCP is not only present in BAT. Similar findings are now reported in the pregnant ovine uterus, where PRLR abundance reaches a maximum just before that of UCP2. However, the role of PRLR in BAT remains undetermined. Rat studies have shown that PRL administration throughout pregnancy results in offspring with increased UCP1 at birth. Studies in newborn lambs have shown that administration of PRL (2 mg/d) causes an acute response, increasing colonic temperature in the first hour by 1 degrees. This increased colonic temperature is maintained for the first 24h of life, in conjunction with enhanced lipolysis. After 7 d of treatment there is no difference in the abundance of UCP1 but an increase in UCP1 activity; this effect may be mediated by an increase in lipolysis. Taken together these findings suggest that PRL could be an important endocrine factor during pregnancy and early postnatal life.

Adipose Tissue, Brown↗
PubMed2005

The mitochondrial uncoupling-protein homologues.

Uncoupling protein(UCP)1 is an integral membrane protein that is located in the mitochondrial inner membrane of brown adipocytes. Its physiological role is to mediate a regulated, thermogenic proton leak. UCP2 and UCP3 are recently identified UCP1 homologues. They also mediate regulated proton leak, and might function to control the production of superoxide and other downstream reactive oxygen species. However, their role in normal physiology remains unknown. Recent studies have shown that UCP2 has an important part in the pathogenesis of type-2 diabetes. The obscure roles of the UCP homologues in normal physiology, together with their emerging role in pathophysiology, provide exciting potential for further investigation.

Carrier Proteins↗
PubMed2002

Adaptive changes in adipocyte gene expression differ in AKR/J and SWR/J mice during diet-induced obesity.

Obesity-prone (AKR/J) and obesity-resistant (SWR/J) mice were weaned onto low (LF) or high fat (HF) diets to identify adaptive changes in adipocyte gene expression that are associated with differences between the strains in fat deposition. Food consumption was monitored at weekly intervals and all mice were evaluated after consuming their respective diets for 4 wk for analysis of mRNA levels of selected metabolic genes. Despite similar food consumption, body weight and fat deposition were significantly greater in AKR/J than in SWR/J mice, and this difference was greatly accentuated by the HF diet. The HF diet produced distinct differences between strains in gene expression patterns among fat depots. In AKR/J mice, UCP1 mRNA was decreased 10-fold in interscapular brown adipose tissue (BAT) and four- to fivefold in retroperitoneal and inguinal white adipose tissue (WAT). The HF diet also decreased PGC-1 and beta(3)-adrenergic receptor mRNA by two- and ninefold in BAT from AKR/J mice. In contrast, the HF diet either increased uncoupling protein (UCP)1 in BAT or had no effect on expression of these genes in adipose tissues from SWR/J mice. UCP2 mRNA was fourfold higher in WAT from AKR/J compared with SWR/J mice and increased by an additional twofold in WAT from AKR/J mice fed the HF diet. UCP2 was unaffected by diet in SWR/J mice. These studies show that the diet-induced obesity of AKR/J mice is characterized by increased metabolic efficiency and is associated with changes in adipocyte gene expression that limit the adaptive thermogenic response to increased energy density.

Adipocytes↗
PubMed2003

Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging.

Brown adipose tissue (BAT; brown fat) is the principal site of adaptive thermogenesis in the human newborn and other small mammals. Of paramount importance for thermogenesis is vascular perfusion, which controls the flow of cool blood in, and warmed blood out, of BAT. We have developed an optical method for the quantitative imaging of BAT perfusion in the living, intact animal using the heptamethine indocyanine IR-786 and near-infrared (NIR) fluorescent light. We present a detailed analysis of the physical, chemical, and cellular properties of IR-786, its biodistribution and pharmacokinetics, and its uptake into BAT. Using transgenic animals with homozygous deletion of Type II iodiothyronine deiodinase, or homozygous deletion of uncoupling proteins (UCPs) 1 and 2, we demonstrate that BAT perfusion can be measured noninvasively, accurately, and reproducibly. Using these techniques, we show that UCP -1/-2 knockout animals, when compared to wild-type animals, have a higher baseline perfusion of BAT but a similar maximal response to beta 3-receptor agonist. These results suggest that compensation for UCP deletion is mediated, in part, by the control of BAT perfusion. Taken together, BAT perfusion can now be measured noninvasively using NIR fluorescent light, and pharmacological modulators of thermogenesis can be screened at relatively high throughput in living animals.

Adipose Tissue, Brown↗
PubMed1998

Chronic central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins.

Continuous (4 days) intracerebroventricular leptin infusion (12 microg/day) was performed in lean rats, and its hormonometabolic effects were determined. Intracerebroventricular leptin administration did not result in leakage of the hormone into the peripheral circulation. Thus, its effects were elicited by its presence within the central nervous system. Intracerebroventricular leptin infusion produced marked decreases in food intake and body weight gain relative to vehicle-infused fed ad libitum rats. Because decreases in food intake alter hormonometabolic homeostasis, additional control rats pair-fed to the amount of food consumed by leptin-infused ones were included in the study. Intracerebroventricular leptin-infused and vehicle-infused pair-fed rats were characterized, relative to vehicle-infused ad libitum-fed animals, by decreases in body weight and insulinemia and by increases in insulin-stimulated overall glucose utilization and muscle and brown adipose tissue glucose utilization index. Brown adipose tissue uncoupling protein (UCP)1, UCP2, and UCP3 mRNA levels were markedly decreased in pair-fed animals relative to those of fed ad libitum control animals, as were liver and white adipose tissue UCP2 and muscle UCP3 mRNA levels. In marked contrast, intracerebroventricular leptin administration was accompanied by the maintenance of high UCP1, UCP2, and UCP3 expression in all these tissues. Thus, despite analogies between leptin's effects and those of pair-feeding with regard to glucose handling, their respective underlying mechanisms differ. While leptin maintains or favors energy-dissipating mechanisms (UCP1, UCP2, and UCP3), the latter are markedly depressed in pair-fed rats. This effect of leptin may prevent subsequent excessive storage processes, thereby maintaining normal body homeostasis.

Adipose Tissue, Brown↗
PubMed2002

Changes in UCP expression in tissues of Zucker rats fed diets with different protein content.

The effect of dietary protein content on the uncoupling proteins (UCP) 1, 2 and 3 expression in a number of tissues of Zucker lean and obese rats was studied. Thirty-day-old male Zucker lean (Fa/?) and obese (fa/fa) rats were fed on hyperproteic (HP, 30% protein), standard (RD, 17% protein) or hypoproteic (LP, 9% protein) diets ad libitum for 30 days. Although dietary protein intake affected the weights of individual muscles in lean and obese animals, these weights were similar. In contrast, huge differences were observed in brown adipose tissue (BAT) and liver weights. Lean rats fed on the LP diet generally increased UCP expression, whereas the HP group had lower values. Obese animals, HP and LP groups showed higher UCP expression in muscles, with slight differences in BAT and lower values for UCP3 in subcutaneous adipose tissue. The mean values of UCP expression in BAT of obese rats were lower than in their lean counterpart, whereas the expression in skeletal muscle was increased. Thus, expression of UCPs can be modified by dietary protein content, in lean and obese rats. A possible thermogenic function of UCP3 in muscle and WAT in obese rats must be taken into account.

Adipose Tissue, Brown↗
PubMed2000

Synergistic activation of UCP-3 expression in cultured fetal rat brown adipocytes by PPARalpha and PPARgamma ligands.

Rat brown adipocytes express mRNAs for Uncoupling Proteins (UCP) 1, 2 and 3 and the Peroxisome Proliferator Activated Receptors (PPAR) alpha and gamma. We have examined the effects of selective PPARalpha or -gamma activation on changes in UCP-1 and UCP-3 mRNA levels in cultured fetal rat brown adipocytes (FBA). Rosiglitazone (1.0 microM), a selective PPARgamma agonist, elicited 5- and 3-fold increases in UCP-1 and UCP-3, respectively. The PPARalpha ligand, Wy14643 (10.0 microM) increased UCP-3 tenfold, but decreased UCP-1. A synergistic effect on UCP-3 expression (30-fold increase; P < 0. 05) was observed when FBA were exposed to a combination of Wy14643 (10.0 microM) and rosiglitazone (10.0 microM). Thus, activation of PPARgamma increases UCP-1 and UCP-3 levels which are differentially regulated by PPARalpha. A synergistic interaction occurs between PPARalpha and PPARgamma in the regulation of UCP-3 in FBA, probably via co-activator recruitment, suppression of co-repressor proteins or through a direct interaction at the level of the PPRE.

Adipose Tissue, Brown↗
PubMed2006

Regulation of UCP1 and UCP3 in arctic ground squirrels and relation with mitochondrial proton leak.

Uncoupling protein (UCP) 1 (UCP1) catalyzes a proton leak in brown adipose tissue (BAT) mitochondria that results in nonshivering thermogenesis (NST), but the extent to which UCP homologs mediate NST in other tissues is controversial. To clarify the role of UCP3 in mediating NST in a hibernating species, we measured Ucp3 expression in skeletal muscle of arctic ground squirrels in one of three activity states (not hibernating, not hibernating and fasted for 48 h, or hibernating) and housed at 5 degrees C or -10 degrees C. We then compared Ucp3 mRNA levels in skeletal muscle with Ucp1 mRNA and UCP1 protein levels in BAT in the same animals. Ucp1 mRNA and UCP1 protein levels were increased on cold exposure and decreased with fasting, with the highest UCP1 levels in thermogenic hibernators. In contrast, Ucp3 mRNA levels were not affected by temperature but were increased 10-fold during fasting and >3-fold during hibernation. UCP3 protein levels were increased nearly fivefold in skeletal muscle mitochondria isolated from fasted squirrels compared with nonhibernators, but proton leak kinetics in the presence of BSA were unchanged. Proton leak in BAT mitochondria also did not differ between fed and fasted animals but did show classical inhibition by the purine nucleotide GDP. Levels of nonesterified fatty acids were highest during hibernation, and tissue temperatures during hibernation were related to Ucp1, but not Ucp3, expression. Taken together, these results do not support a role for UCP3 as a physiologically relevant mediator of NST in muscle.

Adipose Tissue, Brown↗
PubMed1998

UCP2, UCP3 and leptin gene expression: modulation by food restriction and leptin.

To determine the effects of food restriction and leptin administration on several transcripts involved in energy homeostasis, we examined leptin, uncoupling proteins (UCP) 1, 2 and 3, lipoprotein lipase (LPL), beta3-adrenergic receptors (beta3AR) and hormone-sensitive lipase (HSL) mRNA levels in brown adipose tissue (BAT) and epididymal (EWAT) and perirenal (PWAT) white adipose tissue in three groups of rats. The groups were administered leptin for 1 week, or had food restricted to the amount of food consumed by the leptin-treated animals, or had free access to food. Leptin administration increased serum leptin concentrations 50-fold and decreased food consumption by 43%, whereas serum insulin and corticosterone concentrations were unchanged. Leptin increased LPL mRNA by 80%, UCP1 mRNA twofold, and UCP3 mRNA levels by 62% in BAT, and increased UCP2 mRNA levels twofold in EWAT. In contrast, UCP2 mRNA levels were unchanged in PWAT and BAT. In WAT from food-restricted rats, leptin gene expression was diminished by 40% compared with those fed ad libitum. With leptin administration, there was a further 50% decrease in leptin expression. LPL mRNA levels were decreased by food restriction but not by leptin in WAT, whereas beta3AR and HSL mRNA levels were unchanged with either food restriction or leptin treatment. The present study indicates that leptin increases the gene expression of UCP2 in EWAT and that of UCP1, UCP3 and LPL in BAT, whereas reduced food consumption but not leptin, decreases LPL expression in WAT. In addition, with leptin administration there is a decrease in leptin gene expression in WAT, independent of food intake and serum insulin and corticosterone concentrations.

Adipose Tissue↗
PubMed2005

Maternal nutritional programming of fetal adipose tissue development: differential effects on messenger ribonucleic acid abundance for uncoupling proteins and peroxisome proliferator-activated and prolactin receptors.

Maternal nutrient restriction at specific stages of gestation has differential effects on fetal development such that the offspring are programmed to be at increased risk of a range of adult diseases, including obesity. We investigated the effect of maternal nutritional manipulation through gestation on fetal adipose tissue deposition in conjunction with mRNA abundance for uncoupling protein (UCP)1 and 2, peroxisome proliferator-activated receptors (PPAR)alpha and gamma, together with long and short forms of the prolactin receptor (PRLR). Singleton-bearing ewes were either nutrient restricted (3.2-3.8 MJ day(-1) metabolizable energy) or fed to appetite (8.7-9.9 MJ day(-1)) over the period of maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d gestation, ewes were either fed to calculated requirements, (6.7-7.5 MJ day(-1)), or to appetite (8.0-10.9 MJ day(-1)). At term, offspring of nutrient-restricted ewes possessed more adipose tissue, an adaptation that was greatest in those born to mothers that fed to requirements in late gestation. This was accompanied by an increased mRNA abundance for UCP2 and PPARalpha, an adaptation not seen in mothers re-fed to appetite. Maternal nutrition had no effect on mRNA abundance for UCP1, PPARgamma, or PRLR. Irrespective of maternal nutrition, mRNA abundance for UCP1 was positively correlated with PPARgamma and the long and short forms of PRLR, indicating that these factors may act together to ensure that UCP1 abundance is maximized in the newborn. In conclusion, we have shown, for the first time, differential effects of maternal nutrition on key regulatory components of fetal fat metabolism.

Adipose Tissue↗
PubMed2005

Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression.

To further explore the antiobesity effect of freeze-dried bitter melon (BM) juice, activities of mitochondrial lipid oxidative enzymes as well as the expression of uncoupling proteins and their transcription coactivator peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha) were determined in diet-induced obese (DIO) rats. Rats were fed high-fat (HF) diets to induce obesity, and the effect of BM was assessed at doses of 0.75, 1.0, or 1.25% (wt:wt). In a dose-response experiment, BM-supplemented rats had lower energy efficiency (g weight gained/kJ consumed), visceral fat mass, serum glucose, and insulin resistance index, but higher plasma norepinephrine than unsupplemented rats (P < 0.05). Hepatic and skeletal muscle triglyceride concentrations were lower in supplemented HF diet-fed rats than in unsupplemented HF diet-fed rats (P < 0.05). An HF diet supplemented with BM elevated activities of hepatic and muscle mitochondrial carnitine palmitoyl transferase-I (CPT-I) and acyl-CoA dehydrogenase (AD) (P < 0.05). In another experiment, BM (1.0 g/100 g) lowered visceral fat mass but increased serum adiponectin concentration in HF diet-fed rats (P < 0.05). In the final study, rats were fed the HF diet with 0, 1.0 or 1.25% BM. Both groups of BM-supplemented rats had higher uncoupling protein 1 in brown adipose tissue (P < 0.05) and uncoupling protein 3 in red gastrocnemius muscle (P < 0.05), measured by Western blotting and RT-PCR, than the controls. The expression of the transcription coactivator PGC-1alpha in both tissues was also significantly elevated in the BM-supplemented rats (P < 0.05). The present results suggest that decreased adiposity in BM-supplemented rats may result from lower metabolic efficiency, a consequence of increased lipid oxidation and mitochondrial uncoupling.

Acyl-CoA Dehydrogenase↗
PubMed2000

Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice.

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.

Adipose Tissue↗
PubMed2002

Uncoupling of protein-3 induces an uncontrolled uncoupling of mitochondria after expression in muscle derived L6 cells.

The uncoupling proteins (UCPs) are thought to uncouple oxidative phosphorylation in the mitochondria and thus generate heat. One of the UCP isoforms, UCP3, is abundantly expressed in skeletal muscle, the major thermogenic tissue in humans. UCP3 has been overexpressed at high levels in yeast systems, where it leads to the uncoupling of cell respiration, suggesting that UCP3 may indeed be capable of dissipating the mitochondrial proton gradient. This effect, however, was recently shown to be a consequence of the high level of expression and incorrect folding of the protein and not to its intrinsic uncoupling activity. In the present study, we investigated the properties of UCP3 overexpressed in a relevant mammalian host system such as the rat myoblast L6 cell line. UCP3 was expressed in relatively low levels (< 1 microg x mg(-1) membrane protein) with the help of an adenovirus vector. Immunofluorescence microscopy of transduced L6 cells showed that UCP3 was expressed in more than 90% of the cells and that its staining pattern was characteristic for mitochondrial localization. The oxygen consumption of L6 cells under nonphosphorylating conditions increased concomitantly with the levels of UCP3 expression. However, uncoupling was associated with an inhibition of the maximal respiratory capacity of mitochondria and was not affected by purine nucleotides and free fatty acids. Moreover, recombinant UCP3 was resistant to Triton X-100 extraction under conditions that fully solubilize membrane bound proteins. Thus, UCP3 can be uniformly overexpressed in the mitochondria of a relevant muscle-derived cell line resulting in the expected increase of mitochondrial uncoupling. However, our data suggest that the protein is present in an incompetent conformation.

Animals↗
PubMed1999

Mitochondrial proton leak and the uncoupling proteins.

An energetically significant leak of protons occurs across the mitochondrial inner membranes of eukaryotic cells. This seemingly wasteful proton leak accounts for at least 20% of the standard metabolic rate of a rat. There is evidence that it makes a similar contribution to standard metabolic rate in a lizard. Proton conductance of the mitochondrial inner membrane can be considered as having two components: a basal component present in all mitochondria, and an augmentative component, which may occur in tissues of mammals and perhaps of some other animals. The uncoupling protein of brown adipose tissue, UCP1, is a clear example of such an augmentative component. The newly discovered UCP1 homologs, UCP2, UCP3, and brain mitochondrial carrier protein 1 (BMCP1) may participate in the augmentative component of proton leak. However, they do not appear to catalyze the basal leak, as this is observed in mitochondria from cells which apparently lack these proteins. Whereas UCP1 plays an important role in thermogenesis, the evidence that UCP2 and UCP3 do likewise remains equivocal.

Adipose Tissue, Brown↗
PubMed1989

Brown adipose tissue in lean and fat selection lines of sheep identified by immunodetection of uncoupling protein in western blots of tissue homogenates.

1. Uncoupling protein (UCP) was purified from perirenal adipose tissue of 2-day-old lambs by a procedure involving Triton solubilization and hydroxyapatite treatment. It has an apparent Mr of 34,000. 2. Rabbit anti-sheep UCP and rabbit anti-rat UCP each cross-reacted with both rat and sheep UCP in Western blots, indicating that the major antigenic determinants of the sheep UCP and rat UCP are similar. 3. In Western blots, the anti-sheep UCP showed tissue specificity by detecting a band corresponding to UCP only in brown adipose tissue, but not in heart or liver homogenates. 4. The Western blotting procedure was used to analyse sheep tissues. UCP was detected in samples of perirenal, omental, back and lymph node fat from 2-day-old lambs, but not in heart, liver, muscle or kidney samples. 5. UCP was not detected in any tissue samples from 34-day-old or 7-month-old lambs. 6. Comparison of the amount of UCP in perirenal fat of 2-day-old lambs from lean, fat and control selection lines, using the Western blotting procedure, showed no apparent difference.

Adipose Tissue↗
PubMed1998

A selective human beta3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys.

Activation of beta3 adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to up-regulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with beta3 agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus beta3 receptors, we now demonstrate that acute exposure of rhesus monkeys to a beta3 agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for beta3 agonists in the treatment of human obesity.

Adipose Tissue, Brown↗
PubMed2000

Effect of topiramate on body weight and body composition of osborne-mendel rats fed a high-fat diet: alterations in hormones, neuropeptide, and uncoupling-protein mRNAs.

The effects of topiramate on food intake and body composition were investigated in rats fed a high-fat diet and compared with rats that were pair fed or treated with D-fenfluramine. Topiramate (40 mg. kg. d for 80 d) reduced body-weight gain in a manner similar to that of pair-fed rats and D-fenfluramine-treated rats. The reduction in body fat accounted for all the weight reduction after topiramate treatment but not after pair feeding or D-fenfluramine treatment. Topiramate reduced food intake acutely and increased metabolic rate. There were also significant reductions in leptin, insulin, and corticosterone. In the hypothalamus, topiramate increased mRNA for neuropeptide Y, reduced mRNA for neuropeptide-Y Y1 and Y5 receptors, corticotropin-releasing hormone (CRH), and type II glucocorticoid receptors but had no effect on mRNA levels for the short or long form of the leptin receptor. In peripheral tissues, topiramate reduced leptin mRNA in adipose tissue, had no effect on uncoupling protein 1 mRNA in brown adipose tissue but had tissue-selective effects on uncoupling proteins 2 and 3 mRNA levels in white and brown adipose tissues and muscle. In conclusion, topiramate is an effective inhibitor of weight gain in rats on a high-fat diet, but the mechanism through which the change in energy balance is achieved is unclear.

Animals↗
PubMed2005

Fat storage in adipocytes requires inactivation of leptin's paracrine activity: implications for treatment of human obesity.

Hyperleptinemia rapidly depletes adipocyte fat in lean rats, whereas comparable hyperleptinemia produced by adipocytes in diet-induced obesity does not, implying a leptinergic blockade in adipocytes during overnutrition. Indeed, activated STAT-3 in white adipose tissue (WAT) of normal rats was less on a 60% high fat diet (HFD) than on 4% fat, despite a 10-fold higher plasma leptin. In 6 days of a HFD, mRNA of the postreceptor leptin inhibitor, suppressor of cytokine signaling-3, increased 22-fold in WAT, while leptin receptor (Lepr-b) mRNA gradually disappeared, implying leptinergic blockade at both postreceptor and receptor levels. Adipocyte-specific Lepr-b overexpression of a Lepr-b transgene completely prevented the adipocyte hypertrophy and hyperplasia and the increase in body fat induced in wild-type mice by HFD. Activated STAT-3 and AMP-activated protein kinase (AMPK), and the mRNA of lipooxidative enzymes, peroxisome proliferator-activated receptor-gamma-coactivator-1alpha, and uncoupling protein-1 and -2 were increased in WAT. Body temperature was elevated in the transgenic mice, suggesting uncoupled fatty acid oxidation of surplus fatty acids. In conclusion, storage of surplus calories in WAT and the development of diet-induced obesity require the blockade of a latent leptin-stimulated caloric sump in white adipocytes.

Adenylate Kinase↗