Hormone-sensitive Lipase Activity Research Articles

Nutrition-regulated lipolysis in rainbow trout (Oncorhynchus mykiss) is associated with alterations in the ERK, PI3K-Akt, JAK-STAT, and PKC signaling pathways

Previous studies have shown that food deprivation, which occurs naturally in the life cycle of many species of fish, results in cessation of growth and catabolism of stored energy reserves, including lipids. In this study, we used rainbow trout (Oncorhynchus mykiss) to identify the cellular mechanisms involved with this metabolic shift. Fish were placed on one of five dietary regimes—fed continuously for 2 or 4weeks, fasted continuously for 2 or 4weeks, or fasted 2weeks then refed 2weeks—and the effects on organismal growth and lipid catabolism and on the activation state of signaling elements (e.g., Akt, ERK, JAK-STAT, PKC) in selected tissues were measured. Fasting for either 2 or 4weeks significantly retarded growth in terms of body weight, body length, and body condition; refeeding restored growth such that body length and body condition were similar to measures seen in continuously fed fish. Fasting activated lipid catabolism by stimulating the mRNA expression and catalytic activity of hormone-sensitive lipase (HSL). Two HSL-encoding mRNAs have been characterized, and the expression of both forms of mRNA in 2- and 4-week fasted fish were significantly elevated over levels in fed fish in all tissues. In adipose tissue, liver, and white muscle, HSL activity was significantly elevated in 2- and 4-week fasted fish compared to fed animals; whereas in red muscle, HSL activity was significantly elevated compared to fed fish after 4weeks of fasting. Refeeding reversed both fasting-associated HSL mRNA expression and HSL activity. Fasting resulted in the deactivation of Akt, JAK2, and STAT5 in adipose tissue, liver, and red and white muscle. By contrast, fasting activated ERK and PKC in all tissues measured. Refeeding reversed fasting-associated alterations in the activation state of all signal elements. These findings suggest that deactivation of Akt and JAK-STAT in conjunction with activation of ERK and PKC underlie fasting-associated growth retardation and lipolysis.

Serum Amyloid A Induces Lipolysis by Downregulating Perilipin Through ERK1/2 and PKA Signaling Pathways

Serum amyloid A (SAA) is not only an apolipoprotein, but also a member of the adipokine family with potential to enhance lipolysis. The purpose of this study was to explore how SAA facilitates lipolysis in porcine adipocytes. We found that SAA increased the phosphorylation of perilipin and hormone-sensitive lipase (HSL) after 12-h treatment and decreased perilipin expression after 24-h treatment, and these effects were prevented by extracellular signal-regulated kinase (ERK) or protein kinase A (PKA) inhibitors in primary adipocyte cell culture. SAA treatment decreased HSL and adipose triglyceride lipase (ATGL) expression. SAA treatment also activated ERK and PKA by increasing the phosphorylation of these kinases. Moreover, SAA significantly increased porcine adipocyte glycerol release and lipase activity, which was inhibited by either ERK (PD98059) or PKA (H89) inhibitors, suggesting that ERK and PKA were involved in mediating SAA enhanced lipolysis. SAA downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) mRNA, which was reversed by the ERK inhibitor. We performed a porcine perilipin promoter assay in differentiated 3T3-L1 adipocytes and found that SAA reduced the porcine perilipin promoter specifically through the function of its PPAR response element (PPRE), and this effect was reversed by the ERK inhibitor. These findings demonstrate that SAA-induced lipolysis is a result of downregulation of perilipin and activation of HSL via ERK/PPARγ and PKA signaling pathways. The finding could lead to developing new strategies for reducing human obesity.

Effects of dietary dihydropyridine on laying performance and lipid metabolism of broiler breeder hens

The experiment was conducted to investigate the effects of dihydropyridine supplementation on the laying performance and lipid metabolism of broiler breeder hens. A total of 720 forty-five-week old broiler breeder hens were randomly divided into four experimental groups, each group consisting of six replicates of 30 birds. For 10 weeks the birds were fed a maize-soybean meal diet containing 0, 100, 200, 300 mg dihydropyridine/kg, in the respective treatment groups. The daily egg weight and daily feed intake were not affected by dihydropyridine supplementation, but the laying rate and feed efficiency were significantly increased. The percentage of abdominal fat and percentage of liver fat were significantly decreased by dietary dihydropyridine. A level of 100 mg dihydropyridine/kg had no effect on hormone-sensitive triglyceride lipase (HSL) activity in the liver or abdominal fat, though higher levels of dietary dihydropyridine (200 mg/kg or 300 mg/kg) increased HSL activity in the liver and abdominal fat. The concentration of cyclic adenosine monophosphate (cAMP) and superoxide dismutase activity were significantly increased by dihydropyridine, but the malondialdehyde content decreased. The apolipoprotein B concentration was increased at levels of 100 and 200 mg dihydropyridine/kg, but the 300 mg level had no effect on apolipoprotein B, compared with the control group. The triiodothyronine concentration was significantly increased by dietary dihydropyridine. It is concluded that supplementing dihydropyridine in the diet has a beneficial effect on the laying performance and regulates the fat metabolism of broiler breeder hens. The results suggest that the supplementation of 200 mg dihydropyridine/kg diet is the optimal dose for broiler breeder hens.

Healthy Lifestyle Behaviors and Triglycerides

Healthy Lifestyle Behaviors and Triglycerides

Triglyceride with Medium-Chain Fatty Acids Increases the Activity and Expression of Hormone-Sensitive Lipase in White Adipose Tissue of C57BL/6J Mice

We have previously shown that medium-chain triglyceride (MCT) resulted in significantly less body fat mass than long-chain triglyceride (LCT) did in hypertriglyceridimic subjects. The possible mechanism for this was investigated by measuring and analyzing changes in the body fat, blood lipid profile, enzymatic level and activity of hormone-sensitive lipase (HSL) and its mRNA expression, and levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in white adipose tissue (WAT) of C57BL/6J mice fed for 16 weeks on an MCT or LCT diet. MCT induced lower body weight and body fat, and an improved blood lipid profile than LCT did. The enzymatic level and activity of HSL and its mRNA expression, and the levels of cAMP and PKA were significantly higher in WAT of mice fed with the MCT diet. No significant differences in the levels of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in WAT were apparent between the effects of MCT and LCT. It is concluded that lipolysis by the increased level and activity of HSL, which was induced by the activation of cAMP-dependent PKA in WAT, was partially responsible for the lower fat accumulation in C57BL/6J mice fed with MCT.

Fat digestion and absorption in spice-pretreated rats.

A few common spices are known to stimulate secretion of bile with higher amount of bile acids which play a major role in digestion and absorption of dietary lipids. It would be appropriate to verify if these spices enable efficient digestion and absorption during high-fat intake. In this context, dietary ginger (0.05%), piperine (0.02%), capsaicin (0.015%), and curcumin (0.5%) were examined for their influence on bile secretion, digestive enzymes of pancreas and absorption of dietary fat in high-fat (30%) fed Wistar rats for 8 weeks. These spices enhanced the activity of pancreatic lipase, amylase, trypsin and chymotrypsin by 22-57%, 32-51%, 63-81% and 12-38%, respectively. Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content. Stimulation of lipid mobilisation from adipose tissue was suggested by the decrease in perirenal adipose tissue weight by dietary capsaicin and piperine. This was also accompanied by prevention of the accumulation of triglyceride in liver and serum in high-fat fed rats. Activities of key lipogenic enzymes in liver were reduced which was accompanied by an increased activity of hormone-sensitive lipase. Thus, dietary ginger and other spice compounds enhance fat digestion and absorption in high-fat fed situation through enhanced secretion of bile salts and a stimulation of the activity pancreatic lipase. At the same time, the energy expenditure is facilitated by these spices to prevent the accumulation of absorbed fat.

Rye bran alkylresorcinols suppress adipocyte lipolysis and hormone‐sensitive lipase activity

The effects of alkylresorcinols (ARs) isolated from rye bran on adipocyte lipolysis, hormone-sensitive lipase activity and phosphorylation and on phosphorylation of protein kinase A substrates were studied. Preincubation with ARs for 18 h suppressed catecholamine-stimulated lipolysis in 3T3-L1 adipocytes. Furthermore, phosphorylation of hormone-sensitive lipase (HSL), a key lipase responsible for stimulated lipolysis, and phosphorylation of protein kinase A substrates, were diminished after preincubation with ARs, whereas HSL protein expression was unaltered. ARs were also shown to inhibit HSL activity in an in vitro assay.

A potential role of Lavandula angustifolia in the management of diabetic dyslipidemia

Diabetic dyslipidemia is a key contributor to insulin resistance and a risk factor for cardiovascular complications in patients with DM type 2. Lavandula angustifolia (lavender) is native of the northern region of Jordan and has been long used in Jordanian folkloric medicine in the management of diabetes. To our knowledge, this is the first manuscript to study the potential role of the methanolic extract of the plant in the management of diabetic dyslipidemia. Our results demonstrated in vitro inhibitory effects of L. angustifolia on both hormone sensitive lipase (HSL) and pancreatic lipase (PL) activities. The results indicated that lavender extract inhibited HSL activity in a dose dependent manner with an IC50 of 175.5 µg/ml. Likewise, it inhibited the PL activity in a dose dependent manner with an IC50 of 56.5 µg/ml. Such inhibitory activities could be attributed, but is not exclusive, to the presence of rosmarinic acid (IC50 of 125.2 and 51.5 µg/ml for PL and HSL, respectively) and gallic acid (IC50 of 10.1 and 14.5 µg/ml for PL and HSL, respectively) in the extract. Interestingly, the inhibitory pattern of the lavender on the enzymatic activities of HSL and PL matched the inhibitory pattern of orlistat. Key words: Lavender, hormone sensitive lipase, pancreatic lipase, obesity, diabetes mellitus, medicinal plants.

Leucine Deprivation Stimulates Fat Loss via Increasing CRH Expression in the Hypothalamus and Activating The Sympathetic Nervous System

We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis.

Several agents and pathways regulate lipolysis in adipocytes

Adipose tissue is the only tissue capable of hydrolyzing its stores of triacylglycerol (TAG) and of mobilizing fatty acids and glycerol in the bloodstream so that they can be used by other tissues. The full hydrolysis of TAG depends on the activity of three enzymes, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase, each of which possesses a distinct regulatory mechanism. Although more is known about HSL than about the other two enzymes, it has recently been shown that HLS and ATGL can be activated simultaneously, such that the mechanism that enables HSL to access the surface of lipid droplets also permits the stimulation of ATGL. The classical pathway of lipolysis activation in adipocytes is cAMP-dependent. The production of cAMP is modulated by G-protein-coupled receptors of the Gs/Gi family and cAMP degradation is regulated by phosphodiesterase. However, other pathways that activate TAG hydrolysis are currently under investigation. Lipolysis can also be started by G-protein-coupled receptors of the Gq family, through molecular mechanisms that involve phospholipase C, calmodulin and protein kinase C. There is also evidence that increased lipolytic activity in adipocytes occurs after stimulation of the mitogen-activated protein kinase pathway or after cGMP accumulation and activation of protein kinase G. Several agents contribute to the control of lipolysis in adipocytes by modulating the activity of HSL and ATGL. In this review, we have summarized the signalling pathways activated by several agents involved in the regulation of TAG hydrolysis in adipocytes.

Altered skeletal muscle lipase expression and activity contribute to insulin resistance in humans.

OBJECTIVEInsulin resistance is associated with elevated content of skeletal muscle lipids, including triacylglycerols (TAGs) and diacylglycerols (DAGs). DAGs are by-products of lipolysis consecutive to TAG hydrolysis by adipose triglyceride lipase (ATGL) and are subsequently hydrolyzed by hormone-sensitive lipase (HSL). We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance.RESEARCH DESIGN AND METHODSWe first measured lipase expression in vastus lateralis biopsies of young lean (n = 9), young obese (n = 9), and obese-matched type 2 diabetic (n = 8) subjects. We next investigated in vitro in human primary myotubes the impact of altered lipase expression/activity on lipid content and insulin signaling.RESULTSMuscle ATGL protein was negatively associated with whole-body insulin sensitivity in our population (r = −0.55, P = 0.005), whereas muscle HSL protein was reduced in obese subjects. We next showed that adenovirus-mediated ATGL overexpression in human primary myotubes induced DAG and ceramide accumulation. ATGL overexpression reduced insulin-stimulated glycogen synthesis (−30%, P < 0.05) and disrupted insulin signaling at Ser1101 of the insulin receptor substrate-1 and downstream Akt activation at Ser473. These defects were fully rescued by nonselective protein kinase C inhibition or concomitant HSL overexpression to restore a proper lipolytic balance. We show that selective HSL inhibition induces DAG accumulation and insulin resistance.CONCLUSIONSAltogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action. Targeting skeletal muscle lipases may constitute an interesting strategy to improve insulin sensitivity in obesity and type 2 diabetes.

The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene

Neutral lipid storage disease is caused by mutations in the CGI-58 or the PNPLA2 genes. Lipid storage can be detected in various cell types including blood granulocytes. While CGI-58 mutations are associated with Chanarin-Dorfman syndrome, a condition characterized by lipid storage and skin involvement (ichthyosis), mutations in the patatin-like phospholipase domain-containing protein 2 gene (PNPLA2) were reported with skeletal and cardiac muscle disease only. We describe clinical, myopathological, magnetic resonance imaging (MRI), and genetic findings of six patients carrying different recessive PNPLA2 mutations. Pulse-chase labeling of control and patient cells with supplementation of clenbuterol, salmeterol, and dexamethasone was performed in vitro. The patients share a recognizable phenotype with prominent shoulder girdle weakness and mild pelvic girdle and distal muscle weakness, with highly elevated creatine kinase (CK) and cardiomyopathy developing at later stages. Muscle histology invariably reveals massive accumulation of lipid droplets. New muscle or whole-body MRI techniques may assist diagnosis and may become a useful tool to quantify intramuscular lipid storage. Four novel and two previously reported mutations were detected, affecting different parts of the PNPLA2 gene. Activation of hormone-sensitive lipase by beta-adrenergic substances such as clenbuterol appears to bypass the enzymatic block in PNPLA2-deficient patient cells in vitro. PNPLA2 deficiency is a slowly progressive myopathy with onset around the third decade. Cardiac involvement is relatively common at a later stage. Muscle MRI may detect increased lipid in a characteristic distribution, which could be used for monitoring disease progression. Beta-adrenergic agents may be beneficial in improving triacylglycerol breakdown in patients with PNPLA2 mutations.

Fasting and post-prandial adipose tissue lipoprotein lipase and hormone-sensitive lipase in obesity and Type 2 diabetes

Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups - obese with Type 2 diabetes and obese without diabetes - and in non-diabetic normal-weight controls. Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p<0.05) as well as lower mRNA LPL levels. HSL activity was significantly reduced in the 2 groups of obese subjects compared to controls in both fasting condition and 6 h after the meal (p<0.05), while HSL mRNA levels were not different. There were no significant changes between fasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.

Peroxisome Proliferator-activated Receptor-γ Coactivator-1α Controls Transcription of the Sirt3 Gene, an Essential Component of the Thermogenic Brown Adipocyte Phenotype

Sirt3 (silent mating type information regulation 2, homolog 3), a member of the sirtuin family of protein deacetylases with multiple actions on metabolism and gene expression is expressed in association with brown adipocyte differentiation. Using Sirt3-null brown adipocytes, we determined that Sirt3 is required for an appropriate responsiveness of cells to noradrenergic, cAMP-mediated activation of the expression of brown adipose tissue thermogenic genes. The transcriptional coactivator Pgc-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) induced Sirt3 gene expression in white adipocytes and embryonic fibroblasts as part of its overall induction of a brown adipose tissue-specific pattern of gene expression. In cells lacking Sirt3, Pgc-1α failed to fully induce the expression of brown fat-specific thermogenic genes. Pgc-1α activates Sirt3 gene transcription through coactivation of the orphan nuclear receptor Err (estrogen-related receptor)-α, which bound the proximal Sirt3 gene promoter region. Errα knockdown assays indicated that Errα is required for full induction of Sirt3 gene expression in response to Pgc-1α. The present results indicate that Pgc-1α controls Sirt3 gene expression and this action is an essential component of the overall mechanisms by which Pgc-1α induces the full acquisition of a brown adipocyte differentiated phenotype.

Adiponectin Inhibits Lipolysis in Mouse Adipocytes

OBJECTIVEAdiponectin is an adipocyte-derived hormone that sensitizes insulin and improves energy metabolism in tissues. This study was designed to investigate the direct regulatory effects of adiponectin on lipid metabolism in adipocytes.RESEARCH DESIGN AND METHODSBasal and hormone-stimulated lipolysis were comparatively analyzed using white adipose tissues or primary adipocytes from adiponectin gene knockout and control mice. To further study the underlying mechanisms through which adiponectin suppresses lipolysis, cultured 3T3-L1 adipocytes and adenovirus-mediated gene transduction were used.RESULTSSignificantly increased lipolysis was observed in both adiponectin gene knockout mice and primary adipocytes from these mice. Hormone-stimulated glycerol release was inhibited in adiponectin-treated adipocytes. Adiponectin suppressed hormone-sensitive lipase activation without altering adipose triglyceride lipase and CGI-58 expression in adipocytes. Moreover, adiponectin reduced protein levels of the type 2 regulatory subunit RIIα of protein kinase A by reducing its protein stability. Ectopic expression of RIIα abolished the inhibitory effects of adiponectin on lipolysis in adipocytes.CONCLUSIONSThis study demonstrates that adiponectin inhibits lipolysis in adipocytes and reveals a novel function of adiponectin in lipid metabolism in adipocytes.

Intracellular fatty acids suppress β-adrenergic induction of PKA-targeted gene expression in white adipocytes

β-Adrenergic receptor (β-AR) activation elevates cAMP levels in fat cells and triggers both metabolic and transcriptional responses; however, the potential interactions between these pathways are poorly understood. This study investigated whether lipolysis affects β-AR-mediated gene expression in adipocytes. Acute β(3)-adrenergic receptor (β(3)-AR) stimulation with CL 316,243 (CL) increased expression of PKA-targeted genes PCG-1α, UCP1, and NOR-1 in mouse white fat. Limiting lipolysis via inhibition of hormone-sensitive lipase (HSL), a direct target of PKA, sharply potentiated CL induction of PCG-1α, UCP1, and NOR-1. CL also induced greater expression of PKA-targeted genes in white fat of HSL-null mice compared with wild-type littermates, further indicating that HSL activity limits PKA-mediated gene expression. Inhibiting HSL in 3T3-L1 adipocytes also potentiated the induction of PGC-1α, UCP1, and NOR-1 by β-AR activation, as did siRNA knockdown of adipose triglyceride lipase, the rate-limiting enzyme for lipolysis. Conversely, treatments that promote intracellular fatty acid accumulation suppressed induction of PGC-1α and UCP1 through β-AR stimulation. Analysis of β-adrenergic signaling indicated that excessive intracellular fatty acid production inhibits adenylyl cyclase activity and thereby reduces PKA signaling to the nucleus. Lastly, partially limiting lipolysis by inhibition of HSL increased the induction of oxidative gene expression and mitochondrial electron transport chain activity in white adipose tissue and facilitated fat loss in mice treated for 5 days with CL. Overall, our results demonstrate that fatty acids limit the upregulation of β-AR-responsive genes in white adipocytes and suggest that limiting lipolysis may be a novel means of enhancing β-AR signaling.

Altered adipose tissue metabolism in offspring of dietary obese rat dams

To investigate further the mechanisms of developmental programming, we analysed the effects of maternal overnutrition and of postnatal high-fat feeding on adipose tissue metabolism in the offspring. Postnatal changes in serum adiponectin, leptin and TAG [triacylglycerol (triglyceride)] levels, adipose tissue TAGs, fatty acids and enzyme activities were determined in offspring of cafeteria-diet-fed dams during gestation and lactation, weaned on to standard chow or on to cafeteria diet. Obese rats showed higher adiposity (+35% to 85%) as well as a significant increase in serum glucose, insulin, leptin, adiponectin and TAG levels (P<0.01) and adipose tissue LPL (lipoprotein lipase) and GPDH (glycerol-3-phosphate dehydrogenase) activities (P<0.01), compared with control pups at weaning (day 21) and at adulthood (day 90). Adipose HSL (hormone-sensitive lipase) activity was increased only at day 90 (P<0.05), and FAS (fatty acid synthase) activity remained unchanged. The proportions of SFAs (saturated fatty acids) and MUFAs (mono-unsaturated fatty acids) and the Δ(9)-desaturation index were significantly increased (P<0.05), whereas PUFAs (polyunsaturated fatty acids) were decreased (P<0.01) in serum and adipose TAGs of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal overnutrition induced permanent changes in adipose tissue metabolism of the offspring. These pre-existing alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Consequently, adipose adipokines and enzymes could provide a potential therapeutic target, and new investigations in this field could constitute strategies to improve the impact of early-life overnutrition.

Simultaneous POMC gene transfer to hypothalamus and brainstem increases physical activity, lipolysis and reduces adult-onset obesity

Pro-opiomelanocortin (POMC) neurons are identified in two brain sites, the arcuate nucleus of the hypothalamus and nucleus of the solitary tract (NTS) in brainstem. Earlier pharmacological and POMC gene transfer studies demonstrate that melanocortin activation in either site alone improves insulin sensitivity and reduces obesity. The present study, for the first time, investigated the long-term efficacy of POMC gene transfer concurrently into both sites in the regulation of energy metabolism in aged F344xBN rats bearing adult-onset obesity. Pair feeding was included to reveal food-independent POMC impact on energy expenditure. We introduced adeno-associated virus encoding either POMC or green fluorescence protein to the two brain areas in 22-month-old rats, then recorded food intake and body weight, assessed oxygen consumption, serum leptin, insulin and glucose, tested voluntary wheel running, analysed POMC expression, and examined fat metabolism in brown and white adipose tissues. POMC mRNA was significantly increased in both the hypothalamus and NTS region at termination. Relative to pair feeding, POMC caused sustained weight reduction and additional fat loss, lowered fasting insulin and glucose, and augmented white fat hormone-sensitive lipase activity and brown fat uncoupling protein 1 level. By wheel running assessment, the POMC animals ran twice the distance as the Control or pair-fed rats. Thus, the dual-site POMC treatment ameliorated adult-onset obesity effectively, involving a moderate hypophagia lasting ∼60 days, enhanced lipolysis and thermogenesis, and increased physical activity in the form of voluntary wheel running. The latter finding provides a clue for countering age-related decline in physical activity.

Subacute Endotoxemia Induces Adipose Inflammation and Changes in Lipid and Lipoprotein Metabolism in Cats

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence of obesity, is the potential primary cause of IR and metabolic disorders. Cats received increasing iv doses (10-1000 ng/kg(-1) · h(-1)) of LPS (n = 5) or saline (n = 5) for 10 d. Body temperature, proinflammatory and metabolic markers, and insulin sensitivity were measured daily. Tissue mRNA and protein expression were quantified on d 10. LPS infusion increased circulating and tissue markers of inflammation. Based on the homeostasis model assessment, endotoxemia induced transient IR and β-cell dysfunction. At the whole-body level, IR reverted after the 10-d treatment; however, tissue-specific indications of IR were observed, such as down-regulation of adipose glucose transporter 4, hepatic peroxisome proliferative activated receptor-γ1 and -2, and muscle insulin receptor substrate-1. In adipose tissue, increased hormone-sensitive lipase activity led to reduced adipocyte size, concomitant with increased plasma and hepatic triglyceride content and decreased total and high-density lipoprotein cholesterol levels. Prolonged LPS-induced inflammation caused acute IR, followed by long-lasting tissue-specific dysfunctions of lipid-, glucose-, and insulin metabolism-related targets; this ultimately resulted in dyslipidemia but not whole-body IR. Endotoxemia in cats may provide a promising model to study the cross talk between metabolic and inflammatory responses in the development of adipose tissue dysfunction and IR.

Effect of pu‐erh tea on body fat and lipid profiles in rats with diet‐induced obesity

The antiobesity and antihyperlipidaemic effects of pu-erh tea in rats with high fat diet (HFD)-induced obesity were investigated. Male Sprague-Dawley rats were randomly divided into five groups and fed varying diets for an 8-week period: control diet, HFD, and HFD supplemented with low, moderate or high doses of pu-erh tea extract (0.5 g, 2 g and 4 g/kg BW/day, respectively). Pu-erh tea significantly reduced the total body weight and the weight of various adipose pads. Pu-erh tea administration also significantly lowered plasma total cholesterol, triglyceride concentrations and low-density lipoprotein-cholesterol levels in rats with HFD-induced obesity, but did not affect high-density lipoprotein-cholesterol levels. Moreover, pu-erh tea significantly increased lipoprotein lipase, hepatic lipase and hormone-sensitive lipase activities in epididymal fat tissue in rats with HFD-induced obesity. Analysis of real-time reverse transcription-polymerase chain reaction results indicated that pu-erh tea significantly enhanced mRNA levels of hormone-sensitive lipase in rats with HFD-induced obesity. These results suggest that pu-erh tea attenuated visceral fat accumulation and improved hyperlipidemia in a rat model of HFD-induced obesity.