Hormone-sensitive Lipase mRNA Research Articles

Effects of Weight Loss and Aerobic Exercise Training on Adi-Pose Tissue Zinc α2-Glycoprotein and Associated Genes in Obesity.

Zinc α2-glycoprotein (ZAG) has been implicated in fatty acid metabolism and utilization and is lower in obese and higher in cachexic adults compared to those of normal weight. Previous studies suggest that ZAG binds to the beta3-adrenergic receptor (β3AR) to influence fatty acid metabolism in adipose tissue by regulating hormone sensitive lipase (HSL). The purpose of this study is to investigate the effects of a six-month weight loss (WL) or aerobic exercise (AEX) intervention on adipose tissue and skeletal muscle ZAG mRNA levels and protein expression, as well as the expression of β3AR, and HSL. Abdominal adipose tissue (AB) and gluteal adipose tissue (Glut) and vastus lateralis muscle biopsies were performed before and after WL (n = 13) or AEX (n = 13). ZAG, HSL, and β3AR expressions were determined by RT-PCR, and ZAG and HSL plasma levels by ELISA. Body weight decreased by 9.69% (p < 0.001) in WL and did not change with AEX. Maximal oxygen consumption (VO2max) increased by 7.1% (p < 0.005) after WL and by 16.69% (p < 0.001) after AEX. WL significantly decreased body weight with a reduction of percentage of fat, fat mass, fat-free mass (FFM). AEX decreased percent fat and increased VO2max, but did not change fat mass and FFM. Abdominal ZAG and HSL mRNA levels did not change significantly after WL or AEX. There were no changes in plasma ZAG, HSL and adipose tissue β3AR mRNA levels after WL and AEX. ZAG, HSL and β3AR mRNA expressions in adipose tissue are positively associated each other. Adipose tissue abdominal and gluteal HSL are negatively associated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), and both ZAG and HSL adipose tissue are negatively associated with fasting glucose and the glucose area under the curve. Further work is needed to elucidate the role of ZAG and HSL in the propensity for weight gain and the ability of exercise to mitigate these responses.

Kaempferia parviflora rhizome extract exerts anti-obesity effect in high-fat diet-induced obese C57BL/6N mice.

Kaempferia parviflora (KP) rhizome, also called black ginger, has been used as a herbal medicine for many centuries. This current study was aimed at exploring whether KP rhizome extract (KPE) had anti-obesity effects and the mechanism involved. Five-week-old C57BL/6N male mice were allocated into five groups for 8-week feeding with control diet (CD), high-fat diet (HFD), HFD + 150 mg/kg body weight (BW)/day KPE (HFD+K150), HFD + 300 mg/kg BW/day KPE (HFD+K300), and HFD + 600 mg/kg BW/day KPE (HFD+K600). KPE decreased BW, body fat mass, adipose tissue weight, adipocyte size, and serum levels of glucose, triglycerides, cholesterol, insulin, and leptin in HFD-induced obese C57BL/6N mice. KPE inhibited adipogenesis by decreasing CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase 1, ATP-citrate lyase, and fatty acid synthase mRNA expression. KPE improved lipolysis by increasing carnitine palmitoyl transferase 1 and hormone-sensitive lipase mRNA expression. These results suggest that KPE may have inhibited HFD-induced obesity by regulating several pathways involved in decreasing adipogenesis and enhancing lipolysis. Thus, the results suggest that KPE (or KP) may be applicable as an anti-obesity agent.

Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel.

Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelus dromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction.

Dietary copper supplementation enhances lipolysis in Rex rabbits

BackgroundCopper is an important regulator of lipid metabolism in mammals, as a cofactor of many enzymes and is involved in the lipolysis. Copper deficiency has been considered as a significant factor in human diseases related to abnormal lipid metabolism, while adding copper to the diet seems to be the simplest and most effective way to prevent copper deficiency. AimsThe aim of this study was to investigate the effects of dietary copper level on lipid metabolism in Rex Rabbits. MethodsA total of 120 90-d-old Rex Rabbits were randomly allotted into three treatments, with 40 replicates (20 males, 20 females) in each treatment (1 rabbit per replicate). The diets included 1) control (8.4 mg/kg), normal-copper diet (39.1 mg/kg), 3) high-copper diet (67.5 mg/kg). The trial including a one-week adaptation period and a five-week experimental period. ResultThe results showed that copper (39.1 mg/kg) diet increased average daily feed intake (ADFI) (P＜0.05, N = 34), and tended to increase the final body weight (FBW) (P = 0.0556, N = 34). Moreover, dietary copper addition (39.1 and 67.5 mg/kg) significantly increased the foreleg and hindleg weight (P＜0.05, N = 8), and decreased the weight of Perirenal fat and the concentration of triglycerides (TG) in the liver (P＜0.05, N = 8). The concentration of triglycerides (TG), epinephrine (EPI), and glucagon (GC) in serum were obviously higher than that in control group (P＜0.05, N = 8), and the concentration of insulin (INS), and very low-density lipoprotein (VLDL) in serum were significantly decreased (P＜0.05, N = 8). The copper group (39.1 mg/kg) showed up-regulated gene expression levels of carnitine palmitoyl transferases (CPT-1 and CPT-2) and peroxisome proliferator-activated receptor (PPAR-α) in liver (P < 0.05, N = 8) and down-regulated gene expression levels of fatty acid synthase (FAS) and Acetyl-CoA carboxylase (ACC) (P < 0.05, N = 8). In skeletal muscle, CPT-1, CPT-2, PPAR-α, fatty acid transport protein (FATP), fatty acid-binding protein (FABP) and lipoprotein lipase (LPL) levels were significantly up-regulated by copper treatment (P < 0.05, N = 8). Rex Rabbits receiving copper addition had higher CPT-1, CPT-2, PPAR-a and hormone-sensitive lipase (HSL) mRNA levels in adipose tissue (P < 0.05, N = 8). ConclusionCopper diets promoted skeletal muscle growth and reduced fat accumulation by enhancing fatty acid oxidation, at the same time, dietary copper inhibited De novo lipogenesis in the liver. PPAR-α signaling in liver, skeletal muscle and adipose tissues were involved in the regulation of lipid metabolism by copper.

Dietary fat content and adipose triglyceride lipase and hormone-sensitive lipase gene expressions in adults’ subcutaneous and visceral fat tissues

IntroductionWe examined the association of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) gene expressions, as the key regulators of lipolysis, with dietary fat quantity and composition in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). MethodsIn this observational study, samples were collected from patients undergoing elective abdominal surgery. Participants were categorized into two groups based on their body mass index (BMI) status. Dietary, anthropometric, and biochemical data were collected before surgery. Linear regression was performed to determine the association of dietary fat content with ATGL and HSL gene expressions in SAT and VAT. Results152 individuals with a mean ± SD age of 40.7 ± 13.2 years and a median (inter-quartile range) BMI of 39.4 (26.5–45.3 kg/m2) participated in this study, of whom 54 were non-obese (BMI<30 kg/m2), and 98 were obese (BMI≥30 kg/m2). Among non-obese participants, positive associations were observed between ATGL mRNA expression and reported intakes of total fatty acids (TFA) (β=0.306, P = 0.025), myristic (β=0.285, P = 0.038), palmitic (β=0.417, P = 0.002), oleic (β=0.333, P = 0.017), dairy trans (β=0.374, P = 0.006), and other trans FAs (β=0.369, P = 0.006) in SAT. In contrast, inverse associations between HSL mRNA expression and reported intakes of TFAs (β=-0.377, P = 0.005), myristic (β=-0.282, P = 0.039), palmitic (β=-0.372, P = 0.006), stearic (β=-0.314, P = 0.020), and oleic acid (β=-0.372, P = 0.007) were observed in SAT. No associations were observed among obese participants, nor in VAT among non-obese individuals. ConclusionATGL and HSL mRNA expressions in SAT were associated with dietary fat quantity and composition among non-obese adults.

Short-term administration of spexin in rats reduces obesity by affecting lipolysis and lipogenesis: An in vivo and in vitro study

The present study aimed to characterize the role of spexin (SPX) in maintaining glucose and lipid homeostasis in vivo in rats with diet-induced obesity. The in vitro effect of spexin on metabolic and endocrine functions of adipocytes isolated from obese rats was also investigated. The in vivo experiment was conducted on rats with diet-induced obesity and administered with SPX for 7 days. Lipid and carbohydrate parameters, liver markers, and hormonal profile were measured. In in vitro studies, adipocytes isolated from obese rats were used. The effect of SPX on lipolysis, lipogenesis, and leptin secretion from fat cells was assessed. The results showed that short-term administration of SPX causes weight loss, increases insulin sensitivity, and improves the metabolic state of obese rats. The in vitro experiments showed that spexin and its receptors, namely galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3), were expressed in various fat depots and in adipocytes from obese rats. We also found that the addition of spexin increased the basal and isoproterenol-stimulated lipolysis and reduced the basal and insulin-stimulated lipogenesis in adipocytes isolated from obese rats. Molecular analysis showed that SPX activated hormone-sensitive lipase (HSL) phosphorylation and upregulated perilipin and HSL mRNA expression. These results suggest that SPX regulates metabolism of obese rats by affecting lipolysis and lipogenesis in adipocytes. Moreover, the present study for the first time demonstrates that SPX modulates leptin synthesis and secretion from isolated adipocytes.

Amino acids regulate energy utilization through mammalian target of rapamycin complex 1 and adenosine monophosphate activated protein kinase pathway in porcine enterocytes.

As major fuels for the small intestinal mucosa, dietary amino acids (AA) are catabolized in the mitochondria and serve as sources of energy production. The present study was conducted to investigate AA metabolism that supply cell energy and the underlying signaling pathways in porcine enterocytes. Intestinal porcine epithelial cells (IPEC-J2) were treated with different concentrations of AA, inhibitor, or agonist of mammalian target of rapamycin complex 1 (mTORC1) and adenosine monophosphate activated protein kinase (AMPK), and mitochondrial respiration was monitored. The results showed that AA treatments resulted in enhanced mitochondrial respiration, increased intracellular content of pyruvic acid and lactic acid, and increased hormone-sensitive lipase mRNA expression. Meanwhile, decreased citrate synthase, isocitrate dehydrogenase alpha, and carnitine palmitoyltransferase 1 mRNA expression were also observed. We found that AA treatments increased the protein levels of phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated-p70 ribosomal protein S6 kinase, and phosphorylated-4E-binding protein 1. What is more, the protein levels of phosphorylated AMPK α (p-AMPKα) and nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-1 (SIRT1) were decreased by AA treatments in a time depending manner. Mitochondrial bioenergetics and the production of tricarboxylic acid cycle intermediates were decreased upon inhibition of mTORC1 or AMPK. Moreover, AMPK activation could up-regulate the mRNA expressions of inhibitor of nuclear factor kappa-B kinase subunit beta (Ikbkβ), integrin-linked protein kinase (ILK), unconventional myosin-Ic (Myo1c), ribosomal protein S6 kinase beta-2 (RPS6Kβ2), and vascular endothelial growth factor (VEGF)-β, which are downstream effectors of mammalian target of rapamycin (mTOR). The mRNA expressions of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) and 5′-AMP-activated protein kinase subunit gamma-1 (PRKAG1), which are upstream regulators of mTOR, were also up-regulated by AMPK activation. On the other hand, AMPK activation also down-regulated FK506-binding protein 1A (FKBP1A), serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform, phosphatase and tensin homolog (PTEN), and unc-51 like autophagy activating kinase 1 (Ulk1), which are up-stream regulators of mTORC1. Taken together, these data indicated that AA regulated cellular energy metabolism through mTOR and AMPK pathway in porcine enterocytes. These results demonstrated interactions of AMPK and mTORC1 pathways in AA catabolism and energy metabolism in intestinal mucosa cells of piglets, and also provided reference for using AA to remedy human intestinal diseases.

Propionate alleviates high-fat diet-induced lipid dysmetabolism by modulating gut microbiota in mice.

The aims were to examine whether oral sodium propionate supplementation regulate lipid metabolism through modulating gut microbiota. ICR male mice (26·98±0·30g) were randomly assigned to three groups (n=10) and fed control diet (Con), high-fat diet (HFD) and HFD plus propionate (Pro) respectively. In this study, we found that HFD increased the weight of final body, inguinal white adipose tissues (iWAT), epididymal white adipose tissue (eWAT) and perirenal white adipose tissue (pWAT), as well as the adipocyte mean area of iWAT and eWAT in mice (P<0·05), whereas sodium propionate treatment reduced the weight of iWAT and pWAT as well as adipocyte mean area of iWAT in mice fed a HFD (P<0·05). Moreover, in the iWAT, the mRNA expression of lipogenesis genes, including peroxisome proliferator activated receptor γ, acetyl-CoA carboxylase and carnitine palmitoyl transferase-1β, was upregulated by HFD challenge (P<0·05), and the elevation of these genes was nearly reversed to the level of control diet-fed mice by sodium propionate treatment. Meanwhile, sodium propionate treatment increased the hormone-sensitive lipase mRNA expression in the iWAT of HFD-fed mice (P<0·05). High-throughput pyrosequencing of the 16S rRNA demonstrated that sodium propionate treatment significantly recovered the gut microbiota dysbiosis in HFD-fed mice, including the richness and diversity of microbiota and the ratio of Firmicutes to Bacteroidetes. Furthermore, the HFD-induced reductions in colonic levels of butyrate and valerate were reversed by sodium propionate treatment, which also normalized the serum LPS level seen in HFD-fed mice to the levels of the control diet-fed mice. Collectively, these results indicated that sodium propionate treatment could improve lipid metabolism in HFD-fed mice, and the potential mechanisms might be via regulating gut microbiota. We demonstrated for the first time that oral sodium propionate significantly improved HFD-induced dysbiosis of gut microbiota, indicating that the mitigative effect of propionate for HFD-induced lipid dysmetabolism might be mediated by gut microbiota in mice.

Effects of liraglutide on lipolysis and the AC3/PKA/HSL pathway.

BackgroundLiraglutide reduces blood glucose, body weight and blood lipid levels. Hormone-sensitive lipase (HSL) is a key enzyme in lipolysis. Evidence from our and other studies have demonstrated that adenylate cyclase 3 (AC3) is associated with obesity and can be upregulated by liraglutide in obese mice. In the present study, we investigated whether hepatic HSL activity is regulated by liraglutide and characterized the effect of liraglutide in the AC3/protein kinase A (PKA)/HSL signalling pathway.MethodsObese mice or their lean littermates were treated with liraglutide or saline for 8 weeks. Serum was collected for the measurement of insulin and lipids. We investigated hepatic AC3, HSL and phosphorylated HSL Ser-660 (p-HSL(S660)) protein expression levels andAC3 and HSL mRNA expression levels and cyclic adenosine monophosphate (cAMP), PKA activity in liver tissue.ResultsLiraglutide treatment decreased triglycerides (TGs) and free fatty acids (FFAs), increased glycerol, and upregulated hepatic AC3 and p-HSL(s660) levels and cAMP and PKA activities.ConclusionThe results suggest that liraglutide can upregulates AC3/PKA/HSL pathway and may promotes lipolysis.

PO-305 An 8-week, low carbohydrate, high fat, ketogenic diet enhanced exercise capacity through improved ketolysis and lipolysis in mice

PO-305 An 8-week, low carbohydrate, high fat, ketogenic diet enhanced exercise capacity through improved ketolysis and lipolysis in mice

Soy protein supplementation is not androgenic or estrogenic in college-aged men when combined with resistance exercise training

It is currently unclear as to whether sex hormones are significantly affected by soy or whey protein consumption. Additionally, estrogenic signaling may be potentiated via soy protein supplementation due to the presence of phytoestrogenic isoflavones. Limited evidence suggests that whey protein supplementation may increase androgenic signalling. Therefore, the purpose of this study was to examine the effects of soy protein concentrate (SPC), whey protein concentrate (WPC), or placebo (PLA) supplementation on serum sex hormones, androgen signaling markers in muscle tissue, and estrogen signaling markers in subcutaneous (SQ) adipose tissue of previously untrained, college-aged men (n = 47, 20 ± 1 yrs) that resistance trained for 12 weeks. Fasting serum total testosterone increased pre- to post-training, but more so in subjects consuming WPC (p < 0.05), whereas serum 17β-estradiol remained unaltered. SQ estrogen receptor alpha (ERα) protein expression and hormone-sensitive lipase mRNA increased with training regardless of supplementation. Muscle androgen receptor (AR) mRNA increased while ornithine decarboxylase mRNA (a gene target indicative of androgen signaling) decreased with training regardless of supplementation (p < 0.05). No significant interactions of supplement and time were observed for adipose tissue ERα/β protein levels, muscle tissue AR protein levels, or mRNAs in either tissue indicative of altered estrogenic or androgenic activity. Interestingly, WPC had the largest effect on increasing type II muscle fiber cross sectional area values (Cohen’s d = 1.30), whereas SPC had the largest effect on increasing this metric in type I fibers (Cohen’s d = 0.84). These data suggest that, while isoflavones were detected in SPC, chronic WPC or SPC supplementation did not appreciably affect biomarkers related to muscle androgenic signaling or SQ estrogenic signaling. The noted fiber type-specific responses to WPC and SPC supplementation warrant future research.

Lower Stearoyl-CoA Desaturase and Hormone Sensitive Lipase Gene Expression in Superficial Subcutaneous Adipose Tissue of Male, but Not Female, Patients with Type 2 Diabetes

Mitochondrial gene expression in visceral (VAT) and lipogenesis in abdominal subcutaneous adipose tissue (SAT) are lower in insulin resistance (IR). Humans with hormone sensitive lipase (HSL) gene mutations are prone to type 2 diabetes (T2D). SAT is divided into deep (DSAT) and superficial SAT (SSAT). SSAT was speculated to be protective in T2D, but gender specificity is unknown. We hypothesized lower mitochondrial efficiency as well as lower markers of lipogenesis and lipolysis in SSAT only in male T2D patients vs. glucose-tolerant humans (CON), which may characterize dysfunctional SSAT. In 20 T2D and 20 CON matched for sex, BMI and age (female/male: 6/14 per group; 32±1 vs. 31±1 kg/m2, 52±2 vs. 54±2 years), we assessed M-values by euglycemic-hyperinsulinemic clamps, liver fat content (HCL) and VAT by MRS. In biopsies of SSAT, mitochondrial oxidative capacity was measured by respirometry, lipogenesis assessed from stearoyl-CoA desaturase (SCD) mRNA, lipolysis from adipocyte triglyceride lipase (ATGL) and HSL mRNA by RTqPCR. The insulin resistant T2D had 63% and 22% higher HCL (p&amp;lt;0.01) and VAT (p&amp;lt;0.05) than CON. In SSAT, T2D featured 20%, 50%, 70%, 49% reductions in oxidative capacity, SCD, ATGL and HSL mRNA (all p&amp;lt;0.05). Gender segregated analyzes showed higher oxidative capacity only in females, whereas only ATGL was also lower in female T2D vs. CON. In T2D, VAT was 22% lower (p&amp;lt;0.01) and HSL mRNA 70% higher (both p&amp;lt;0.001) in female than in male participants. In conclusion, lower lipogenesis and lipolysis in SSAT of male T2D patients may lead to inadequate lipid storage in SSAT, thereby promoting ectopic fat storage as HCL and VAT. Disclosure K. Bódis: None. J. Lundbom: None. T. Jelenik: None. D.F. Markgraf: None. A. Strom: None. O.P. Zaharia: None. Y. Karusheva: None. V. Burkart: None. K. Müssig: None. Y. Kupriyanova: None. M. Ouni: None. J. Hwang: None. D. Ziegler: None. A. Schuermann: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. J. Szendroedi: None.

Identification of the bovine HSL gene expression profiles and its association with fatty acid composition and fat deposition traits

Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of hydrolysing a variety of esters and is considered to be a candidate gene affecting fat deposition traits. Gene expression profiles of HSL were analysed in various adipose tissues of cattle, and the effect of HSL on lipid metabolism genes was analysed by a PCR array. Novel polymorphisms were identified within the HSL regulatory domain by sequencing, and the relationship between HSL variants and fat deposition traits was analysed. HSL mRNA was highly expressed in the subcutaneous and visceral fat of cattle. CPT1B/CPT1C and other lipocatabolic genes were upregulated, and lipogenesis-related genes (FASN, LPL and ACOT12) were downregulated by HSL overexpression in BFFs. Five novel variants in the HSL functional domain were significantly associated with fat deposition traits, including FCR, LBT, MFW and fatty acid composition. HSL plays a pivotal role in the regulation of lipolysis and fatty acid biosynthesis in beef cattle.

Insulin and insulin-like growth factor-1 modulate the lipolytic action of growth hormone by altering signal pathway linkages

Growth hormone (GH) has many actions in vertebrates, including the regulation of two disparate metabolic processes: growth promotion (anabolic) and the mobilization of stored lipids (catabolic). Our previous studies showed that GH stimulated IGF-1 production in hepatocytes from fed rainbow trout, but in cells from fasted fish GH stimulated lipolysis. In this study, we used rainbow trout (Oncorhynchus mykiss) to elucidate regulation of the mechanisms that enable cells to alter their lipolytic responsiveness to GH. In the first experiment, cells were removed from either fed or fasted fish, conditioned in medium containing serum (10%) from either fed or fasted fish, then challenged with GH. GH stimulated the expression of hormone sensitive lipase (HSL), the primary lipolytic enzyme, in cells from fasted fish conditioned with “fasted serum” but not in cells from fasted fish conditioned in “fed serum.” Pretreatment of cells from fed fish with “fasted serum” resulted in GH-stimulated HSL expression, whereas GH-stimulated HSL expression in cells from fasted fish was blocked by conditioning in “fed serum.” The nature of the conditioning serum governed the signaling pathways activated by GH irrespective of the nutritional state of the animals from which the cells were removed. When hepatocytes were pretreated with “fed serum,” GH activated JAK2, STAT5, Akt, and ERK pathways; when cells were pretreated with “fasted serum,” GH activated PKC and ERK. In the second study, we examined the direct effects of insulin (INS) and insulin-like growth factor (IGF-1), two nutritionally-regulated hormones, on GH-stimulated lipolysis and signal transduction in isolated hepatocytes. GH only stimulated HSL mRNA expression in cells from fasted fish. Pretreatment with INS and/or IGF-1 abolished this lipolytic response to GH. INS and/or IGF-1 augmented GH activation of JAK2 and STAT5 in cells from fed and fasted fish. However, INS and/or IGF-1 eliminated the ability of GH to activate PKC and ERK from fasted cells. These results indicate that INS and IGF-1 determine the signaling pathways activated by GH and whether or not a lipolytic response ensues. Such hormone-receptor-signal pathway linkages provide insight into the molecular basis of GH multifunctionality and into how cellular responses to GH can be adjusted to meet physiological (e.g., nutritional), developmental, or other conditions.

Modulation of Fatty Acid Oxidation and Glucose Uptake by Oxytocin in Adipocytes

Oxytocin (OT) is a hypothalamic neuropeptide synthesized and secreted by OT neurons. In addition to its conventional role in reproductive physiology, central OT also regulates various social behaviors, such as care, trust, and emotions. Central and subcutaneous OT infusions stimulate lipid metabolism in mice and rats when fed standard or high fat diets. Mice lacking the OT receptor (OTR) or OT peptide develop late-onset obesity with greater fat pad weights, larger adipocyte size and elevated plasma levels of leptin. To study the effects of OT on lipid metabolism, we examined the effects of serial OT doses (0, 10, 30, 100, 150, 300 nM) on 3T3L1 adipocytes, together with long (144 hours, 6 days) and short (24 hours, 1 day) term treatments. The short-term treatment with 150 nM OT increased triacylglycerol (TAG) accumulation and decreased mRNA expressions of carnitine palmitoyltransferase 1α (CPT-1α) and fatty acid binding protein 4 (FABP4). After long-term incubation with 150 nM OT, only the CPT-1α mRNA was decreased. In differentiated adipocytes derived from pig adipose tissue stem cells, only hormone sensitive lipase mRNA was decreased after short- or long-term treatment with OT. To obtain further insight into the underlying mechanism of OT induction, we tested the involvement of the AKT/PKB pathway; however, AKT phosphorylation was decreased after treatment with 150 nM OT, suggesting that OT effects may be independent from the AKT/PKB pathway. Taken together, OT effects on adipocyte glucose and lipid metabolism are probably through mechanisms other than the AKT/PKB pathway.

Effect of dietary copper addition on lipid metabolism in rabbits

ABSTRACTThe present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0.05). Copper treatment significantly increased gene expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle, CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were involved in the regulation of lipid metabolism by copper.

Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women.

The goal of this study was to determine the effect of acute transdermal 17β‐oestradiol (E2) on the adipogenic potential of subcutaneous adipose‐derived stem cells (ASC) in post‐menopausal women. Post‐menopausal women (n = 11; mean age 57 ± 4.5 years) were treated for 2 weeks, in a randomized, cross‐over design, with transdermal E2 (0.15 mg) or placebo patches. Biopsies of abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) were obtained after each treatment and mature adipocytes were analysed for cell size and ASC for their capacity for proliferation (growth rate), differentiation (triglyceride accumulation) and susceptibility to tumour necrosis factor alpha‐induced apoptosis. Gene expression of oestrogen receptors α and β (ESR1 and ESR2), perilipin 1 and hormone‐sensitive lipase (HSL), was also assessed. In FEM SAT, but not AB SAT, 2 weeks of E2 significantly (P = 0.03) increased ASC differentiation and whole SAT HSL mRNA expression (P = 0.03) compared to placebo. These changes were not associated with mRNA expression of oestrogen receptors α and β, but HSL expression was significantly increased in FEM SAT with transdermal E2 treatment. Adipose‐derived stem cells proliferation and apoptosis did not change in either SAT depot after E2 compared with placebo. Short‐term E2 appeared to increase the adipogenic potential of FEM, but not AB, SAT in post‐menopausal women with possible implications for metabolic disease. Future studies are needed to determine longer term impact of E2 on regional SAT accumulation in the context of positive energy imbalance.

Aerobic Training Decrease Body Fat may via Zinc Alpha2 Glycoprotein

Previous studies have reported that aerobic training reduces body fat content. Zinc alpha2 glycoprotein (ZAG), a lipid mobilizing factor, is negatively correlated with fat mass. The function of ZAG is associated with reduced fatty acid synthase (FAS) expression and increased hormone-sensitive lipase (HSL) expression in liver of obese mice. We hypothesized that aerobic training up-regulate the expression of ZAG, leading to reduction of body fat. PURPOSE: To determine the underlying association between aerobic training and the expression of ZAG. METHODS: High-fat-diet (HFD)-induced obese mice were divided into two groups, control group (C, n=10) and aerobic training group (T, n=10). Training protocol is 8 weeks moderate intensity treadmill running (10m/min for the first four weeks, 12m/min for the last four weeks, 60min/day, 5 days/week). Measure the body weight twice a week. After 8 weeks intervention experiment, , all animals were sacrificed following overnight fasting, the visceral adipose tissue were dissected and weighed, and liver tissue were excised and homogenized. ZAG, FAS and HSL mRNA expression were detected by PCR technique. Data were analyzed by student’s t-test, with statistical significance being set at p ≤ 0.05. RESULTS: Aerobic training decrease body weight (C,76.80±7.13g vs. T,69.50±3.64g, p<0.05), and also reduce visceral adipose weight (C,5.14±1.29g vs.T,2.81±1.53g, p<0.05). Aerobic training increase ZAG mRNA expression in adipose tissue (C,1.26±0.31 vs. T,2.53±0.58,p<0.05) , but it doesn’t change in liver (C,0.95±0.24 vs.T,0.99±0.29,p>0.05). FAS expression in liver decreased (C,0.037±0.016 vs. T,0.106±0.006, p<0.05), HSL expression in liver slightly increased (C,0.0078±0.0017 vs. T,0.0087±0.0024, p>0.05). CONCLUSION: These indicated that aerobic training may increase ZAG mRNA expression in adipose tissue, and ZAG prohibits fat synthesis through decrease FAS mRNA expression. Aerobic training decrease body fat may via ZAG, but the detail mechanism requires future trials to confirm.

Trace Mineral Overload Induced Hepatic Oxidative Damage and Apoptosis in Pigs with Long-Term High-Level Dietary Mineral Exposure.

The present study investigated the effects of dietary trace mineral (Cu, Fe, Mn, and Zn) supplemental strategies on liver oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis of pigs. A total of 96 Duroc × Landrace × Yorkshire (DLY) piglets were randomly divided into four groups: considered or not considered the trace mineral concentrations in basal diet, and then added to the requirements proposed by NRC (2012) (+B/NR or -B/NR); and considered or not considered the basal diet's trace mineral concentrations and then added to the level of commercial trace mineral supplement (+B/PL or -B/PL). Pigs were fed from 6.5 to 115 kg. Compared with +B/NR diets, -B/PL diets increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations (P < 0.05), resulted in high levels of Fe, Cu, Mn, and Zn accumulation in liver (P < 0.05), as well as led to hepatic oxidative damage with the high concentrations of thiobarbituric acid reactive substance (TBARS), protein carbonylation (PCO), and 8-hydroxyguanine (8-OHG) in liver (P < 0.05). Furthermore, pigs fed -B/PL diets increased CCAAT/enhancer-binding protein homologous protein (CHOP), eukaryotic initiation factor-2α (eIF-2a), interleukin-6(IL-6), B-cell lymphoma leukemia-2-associated X protein (Bax), and caspase-3, caspase-8, and caspase-9 gene expression (P < 0.05) in liver. -B/PL diets also up-regulated hepatic mRNA expression of phosphoenolpyruvate carboxykinase1 (PEPCK1), glucose-6-phosphatase (G6PC), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) (P < 0.05) and down-regulated hormone-sensitive lipase (HSL) mRNA expression (P < 0.05) when compared with those of the + B/NR diet group. Taken together, the results indicated that long-term dietary mineral exposure with the commercial supplement level could cause harm to the structure and metabolic function of liver in pigs.

Korean Curcuma longa L. induces lipolysis and regulates leptin in adipocyte cells and rats.

BACKGROUND/OBJECTIVESTurmeric (Curcuma longa L.) has been reported to have many biological functions including anti-obesity. Leptin, peptide hormone produced by adipocytes and its concentration is increased in proportion to the amount of the adipocytes. In the present study, we examined the effects of Korean turmeric on the regulation of adiposity and leptin levels in 3T3-L1 adipocytes and rats fed a high-fat and high-cholesterol diet.MATERIALS/METHODSLeptin secretion, free fatty acid and glycerol contents in 3T3-L1 adipocytes were measured after incubation of cells with turmeric for 24 hours. Rats were divided into four experimental groups: a normal diet group (N), a high-fat and high-cholesterol diet group (HF), a high-fat and high-cholesterol diet group supplemented with 2.5% turmeric extracts (TPA group) and a high-fat and high-cholesterol diet group supplemented with 5% turmeric extracts (TPB group). Serum samples were used for the measurement of leptin concentration.RESULTSContents of free fatty acid and glycerol showed concentration dependent increase in response to turmeric extracts. Effects of turmeric extracts on reduction of lipid accumulation in 3T3-L1 cells were examined by Oil Red O staining. Treatment with turmeric extracts resulted in increased expression levels of adipose triglyceride lipase and hormone-sensitive lipase mRNA. The concentration of leptin from 3T3-L1 adipocytes was significantly decreased by turmeric. Proportional abdominal and epididymal fats weights of the turmeric 5% supplemented group, TPB has significantly decreased compared to the HF group. The serum levels of leptin in the TPA and TPB groups were significantly lower than those of the HF group.CONCLUSIONSBased on these results, we suggested that Korean turmeric may contribute to the decreasing of body fat and regulating leptin secretion.