Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Objectives: The goal of the current study is to determine whether the β-adrenoreceptor (β-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human β1-, β2-, β3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the β3-AR with higher affinity (Kd 46 ± 1 nM) than the β2-AR (Kd 71 ± 3 nM) while there was no binding to the β1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various β-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of β3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of β1- and β2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific β-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a β-3AR, or possibly a β2-AR.     

饲粮中添加杜仲叶对断奶仔猪生长性能、抗氧化力和免疫功能的影响

在断奶仔猪饲粮中添加不同形式的杜仲叶,研究其对仔猪生长性能、腹泻率、抗氧化力及免疫功能的影响,以评估它们在养殖初期替代抗生素的能力。将断奶仔猪(杜×长×大)随机分成对照组、抗生素组(75 mg/kg金霉素)和三个杜仲叶组(杜仲叶提取物、发酵杜仲叶、杜仲叶干粉),每组10头,进行28天养殖试验。结果表明:与对照相比,杜仲叶提取物组仔猪平均日增重(ADG)显著提高并降低料重比(F/G)(P<0.05);与抗生素组相比,杜仲叶提取物组和杜仲叶发酵组ADG和F/G均无显著差异(P>0.05);各组之间平均日采食量(ADFI)差异不显著(P>0.05)。与对照组相比,抗生素组和杜仲叶提取物组仔猪腹泻率显著降低(P<0.05)。与对照组相比,抗生素组和三种杜仲叶组均降低仔猪血液丙二醛含量和提高总抗氧化力(P<0.01),而抗生素组、杜仲叶提取物组和杜仲叶发酵组还显著提高血液免疫球蛋白IgM含量(P<0.01),且表现出提高血液IgG含量的趋势(P=0.06)。与其他各组相比,杜仲叶提取物组可显著提高肝脏指数(P<0.05);肝脏重量、脾脏重量和脾脏指数在各组之间无显著差异(P>0.05)。饲粮中添加杜仲叶提取物可改善断奶仔猪的生长性能,降低腹泻率,提高仔猪抗氧化力和免疫功能,其效果优于发酵杜仲叶和杜仲叶干粉,并具备一定的抗生素替代潜力。     

Hypoglycemic effects of MDG-1, a polysaccharide derived from Ophiopogon japonicas, in the ob/ob mouse model of type 2 diabetes mellitus

Ophiopogon japonicus is a traditional Chinese medicine used to treat diabetes mellitus. We investigate the anti-ischemic properties of a water-soluble β-d-fructan (MDG-1) from O. japonicus, and assess the antidiabetic effects of MDG-1. In the study, ob/ob mice were treated with 150 mg/kg or 300 mg/kg MDG-1 by gavage for 23 d. Blood glucose levels were measured regularly. An oral glucose tolerance test (OGTT) was preformed on day 21. The levels of insulin, total cholesterol and triglyceride in the serum were measured at the end of administration. The liver triglyceride content and tissue weights were also determined. Results show that MDG-1 (300 mg/kg) was demonstrated to exert acute and long-term hypoglycemic effects on fed blood glucose in ob/ob mice. However, only a marginal hypoglycemic effect on fasting blood glucose levels was observed. MDG-1 (300 mg/kg) improved oral glucose tolerance and reduced serum insulin levels and triglyceride content in the liver in ob/ob mice. Furthermore, a reduction in body weight gain and the weight of subcutaneous fat were observed following treatment with MDG-1 (150 mg/kg) compared with the control group. MDG-1 had no significant effects on the total cholesterol and triglyceride levels, food intake and other adipose and organ tissues. These data suggest that MDG-1 exhibits hypoglycemic activity and reduces insulin resistance.     

Abscisic acid root and leaf concentration in relation to biomass partitioning in salinized tomato plants

Salinization is one of the most important causes of crop productivity reduction in many areas of the world. Mechanisms that control leaf growth and shoot development under the osmotic phase of salinity are still obscure, and opinions differ regarding the Abscisic acid (ABA) role in regulation of biomass allocation under salt stress. ABA concentration in roots and leaves was analyzed in a genotype of processing tomato under two increasing levels of salinity stress for five weeks: 100 mM NaCl (S10) and 150 mM NaCl (S15), to study the effect of ABA changes on leaf gas exchange and dry matter partitioning of this crop under salinity conditions. In S15, salinization decreased dry matter by 78% and induced significant increases of Na⁺ and Cl⁻ in both leaves and roots. Dry matter allocated in different parts of plant was significantly different in salt-stressed treatments, as salinization increased root/shoot ratio 2-fold in S15 and 3-fold in S15 compared to the control. Total leaf water potential (Ψ_w) decreased from an average value of approximately −1.0 MPa, measured on control plants and S10, to −1.17 MPa in S15. In S15, photosynthesis was reduced by 23% and stomatal conductance decreased by 61%. Moreover, salinity induced ABA accumulation both in tomato leaves and roots of the more stressed treatment (S15), where ABA level was higher in roots than in leaves (550 and 312 ng g⁻¹ fresh weight, respectively). Our results suggest that the dynamics of ABA and ion accumulation in tomato leaves significantly affected both growth and gas exchange-related parameters in tomato. In particular, ABA appeared to be involved in the tomato salinity response and could play an important role in dry matter partitioning between roots and shoots of tomato plants subjected to salt stress.     

Wasabi leaf extracts attenuate adipocyte hypertrophy through PPARγ and AMPK

Hypertrophy of adipocytes in obese adipose tissues causes metabolic abnormality by adipocytokine dysregulation, which promotes type 2 diabetes mellitus, hypertension, and dyslipidemia. We investigated the effects of wasabi (Wasabia japonica Matsum) leaf extracts on metabolic abnormalities in SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a model of metabolic syndrome. Male SHRSP/ZF rats aged 7 weeks were divided into two groups: control and wasabi leaf extract (WLE) groups, which received water or oral treatment with 4 g/kg/day WLE for 6 weeks. WLE improved the body weight gain and high blood pressure in SHRSP/ZF rats, and the plasma triglyceride levels were significantly lower in the WLE group. Adipocyte hypertrophy was markedly prevented in adipose tissue. The expression of PPARγ and subsequent downstream genes was suppressed in the WLE group adipose tissues. Our data suggest that WLE inhibits adipose hypertrophy by suppressing PPARγ expression in adipose tissue and stimulating the AMPK activity by increased adiponectin.     

Acute reduction of serum leptin level by dietary conjugated linoleic acid in Sprague-Dawley rats

The purpose of this study was to clarify the effect of conjugated linoleic acid on lipid accumulation in adipose tissue. Sprague-Dawley rats were fed a diet containing 2% conjugated linoleic acid for 1, 3, 6, and 12 weeks. In rats fed 2% conjugated linoleic acid, the weight of perirenal white adipose tissue was comparable with that of rats fed a conjugated linoleic acid-free diet. For fatty acid composition of perirenal white adipose tissue, both 16:1/16:0 and 18:1/18:0 ratios were significantly lower in the conjugated linoleic acid-fed group than the control group. Although there was no remarkable difference in serum triglyceride, total cholesterol, and phospholipid levels between dietary groups, serum leptin level was significantly lower than the control group, and lipid content in the perirenal white adipose tissue exerted a tendency toward low compared to the control value at 1-week feeding. On the other hand, leptin level in perirenal white adipose tissue was significantly lower in the conjugated linoleic acid-fed group than the control group at 12-week feeding. In conclusion, these observations suggest dietary conjugated linoleic acid is an acute reducer of serum leptin level. This may afford an explanation of the mechanism of anti-obesity effect in conjugated linoleic acid.     

Green tea catechins prevent obesity through modulation of peroxisome proliferator-activated receptors

Epidemiological evidence and experimental studies suggest that drinking green tea is associated with a lower risk of obesity and related diseases. However, the mechanisms of these effects are not clear. In the present study, we investigated the anti-obesity mechanisms of green tea catechins (GTCs) through modulation of peroxisome proliferator activated-receptor (PPAR) pathways in high-fat diet-induced obesity in rats. GTC supplementation significantly attenuated the increased body and liver weights and the elevated serum and liver triglyceride levels. Meanwhile, GTCs increased the PPARγ levels in subcutaneous white adipose tissue (SWAT) and decreased the PPAR levels in visceral white adipose tissue (VWAT). In addition, GTC treatment up-regulated the levels of PPARδ in SWAT, VWAT, and brown adipose tissue and increased the expression of genes involved in fatty acid oxidation in brown adipose tissue. Our results suggest that GTCs exert their anti-obesity mechanism in part by modulating PPAR signaling pathways.     

Dietary n-6 PUFA deprivation for 15 weeks reduces arachidonic acid concentrations while increasing n-3 PUFA concentrations in organs of post-weaning male rats

Few studies have examined effects of feeding animals a diet deficient in n-6 polyunsaturated fatty acids (PUFAs) but with an adequate amount of n-3 PUFAs. To do this, we fed post-weaning male rats a control n-6 and n-3 PUFA adequate diet and an n-6 deficient diet for 15 weeks, and measured stable lipid and fatty acid concentrations in different organs. The deficient diet contained nutritionally essential linoleic acid (LA,18:2n-6) as 2.3% of total fatty acids (10% of the recommended minimum LA requirement for rodents) but no arachidonic acid (AA, 20:4n-6), and an adequate amount (4.8% of total fatty acids) of α-linolenic acid (18:3n-3). The deficient compared with adequate diet did not significantly affect body weight, but decreased testis weight by 10%. AA concentration was decreased significantly in serum (− 86%), brain (− 27%), liver (− 68%), heart (− 39%), testis (− 25%), and epididymal adipose tissue (− 77%). Eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) concentrations were increased in all but adipose tissue, and the total monounsaturated fatty acid concentration was increased in all organs. The concentration of 20:3n-9, a marker of LA deficiency, was increased by the deficient diet, and serum concentrations of triacylglycerol, total cholesterol and total phospholipid were reduced. In summary, 15 weeks of dietary n-6 PUFA deficiency with n-3 PUFA adequacy significantly reduced n-6 PUFA concentrations in different organs of male rats, while increasing n-3 PUFA and monounsaturated fatty acid concentrations. This rat model could be used to study metabolic, functional and behavioral effects of dietary n-6 PUFA deficiency.     

Cinnamic acid pretreatment mitigates chilling stress of cucumber leaves through altering antioxidant enzyme activity

To elucidate the physiological mechanism of chilling stress mitigated by cinnamic acid (CA) pretreatment, a cucumber variety (Cucumis sativus cv. Jinchun no. 4) was pretreated with 50 μM CA for 2 d and was then cultivated at two temperatures (15/8 and 25/18 °C) for 1 d. We investigated whether exogenous CA could protect cucumber plantlets from chilling stress (15/8 °C) and examined whether the protective effect was associated with the regulation of antioxidant enzymes and lipid peroxidation. At 2 d, exogenous CA did not influence plant growth, but induced the activities of some antioxidant enzymes, including superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), guaiacol peroxidase (GPX, EC 1.11.1.7), glutathione peroxidase (GSH-Px, EC 1.6.4.2) and ascorbate peroxidase (APX, EC 1.11.1.11) in cucumber leaves, and it also elevated the contents of reduced glutathione (GSH) and ascorbate (AsA). When CA was rinsed and the CA-pretreated seedlings were exposed to different temperatures, the antioxidant activities in leaves at 3 d had undergone additional change. Chilling increased the activities of CAT, GSH-PX, APX, GSH and AsA in leaves, but the combination of CA pretreatment and chilling enhanced the antioxidant activities even more. Moreover, chilling inhibited plant growth and increased the contents of malonaldehyde (MDA), superoxide radical (O₂⁻) and hydrogen peroxide (H₂O₂) in cucumber leaves, and the stress resulted in 87.5% of the second leaves being withered. When CA pretreatment was combined with the chilling stress, we observed alleviated growth inhibition and decreased contents of MDA, H₂O₂ and O₂⁻ in comparison to non-pretreated stressed plants, and found that the withered leaves occurred at a rate of 25.0%. We propose that CA pretreatment increases antioxidant enzyme activities in chilling-stressed leaves and decreases lipid peroxidation to some extent, enhancing the tolerance of cucumber leaves to chilling stress.     

Dietary eicosapentaenoic acid supplementation accentuates hepatic triglyceride accumulation in mice with impaired fatty acid oxidation capacity

Reduced mitochondrial fatty acid (FA) β-oxidation can cause accumulation of triglyceride in liver, while intake of eicosapentaenoic acid (EPA) has been recommended as a promising novel therapy to decrease hepatic triglyceride content. However, reduced mitochondrial FA β-oxidation also facilitates accumulation of EPA. To investigate the interplay between EPA administration, mitochondrial activity and hepatic triglyceride accumulation, we investigated the effects of EPA administration to carnitine-deficient mice with impaired mitochondrial FA β-oxidation. C57BL/6J mice received a high-fat diet supplemented or not with 3% EPA in the presence or absence of 500 mg mildronate/kg/day for 10 days. Liver mitochondrial and peroxisomal oxidation, lipid classes and FA composition were determined. Histological staining was performed and mRNA level of genes related to lipid metabolism and inflammation in liver and adipose tissue was determined. Levels of pro-inflammatory eicosanoids and cytokines were measured in plasma. The results showed that mildronate treatment decreased hepatic carnitine concentration and mitochondrial FA β-oxidation and induced severe triglyceride accumulation accompanied by elevated systemic inflammation. Surprisingly, inclusion of EPA in the diet exacerbated the mildronate-induced triglyceride accumulation. This was accompanied by a considerable increase of EPA accumulation while decreased total n-3/n-6 ratio in liver. However, inclusion of EPA in the diet attenuated the mildronate-induced mRNA expression of inflammatory genes in adipose tissue. Taken together, dietary supplementation with EPA exacerbated the triglyceride accumulation induced by impaired mitochondrial FA β-oxidation. Thus, further thorough evaluation of the potential risk of EPA supplementation as a therapy for NAFLD associated with impaired mitochondrial FA oxidation is warranted.     

Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor δ (PPARδ) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARδ protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. Consistent with the in vitro results, PRPA activated AMPK signaling and altered the expression of lipid metabolism-related proteins in liver and skeletal muscle. Taken together, these findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK and PPARδ, and regulate lipid metabolism, suggesting their potential anti-obesity effects.     

Voglibose administration regulates body weight and energy intake in high fat-induced obese mice

We tested whether long-term administration of voglibose (VO) prevents diet induced obesity in addition to hypoglycemic effects in high fat fed mice and further investigated the underlying mechanisms by which voglibose exerts its weight lowering effect. Male C57BL/6 mice were fed ad libitum for 12 weeks with the control diet (CTL), high-fat diet (HFD) or the HFD with VO supplementations. Blood lipid profile, plasma leptin levels and hepatic triglyceride content, as well as expressions of genes involved in appetite and mitochondrial function were examined. The results showed that VO significantly reduced body weight, fat mass and energy intakes in high fat fed mice. VO showed improved metabolic profiles including blood glucose, triglyceride and free fatty acid. Elevated levels of plasma leptin in HFD were significantly reduced with the VO, furthermore, VO modulated the hypothalamic expressions of leptin receptors and appetite related genes. VO showed the upregulated expressions of PGC-1 in the liver and epididymal adipose tissue. In conclusion, VO may exert antiobesity properties through reductions in energy intake and improvement in mitochondrial function, indicating that VO has potential therapeutic use in patients with obesity, type 2 diabetes, and related complications.     

Resistance to age-related, normal body weight gain in RGS2 deficient mice

RGS2 (regulator of G protein signaling 2) is known to limit signals mediated via Gq- and Gs-coupled GPCRs (G protein coupled receptors), and it has been implicated in the differentiation of several cells types. The physiology of RGS2 knockout mice (rgs2^−/−) has been studied in some detail, however, a metabolic phenotype has not previously been reported. We observed that old (21-24 month) rgs2^−/− mice weigh much less than wild-type C57BL/6 controls, and exhibit greatly reduced fat deposits, decreased serum lipids, and low leptin levels. Lower weight was evident as early as four weeks and continued throughout life. Younger adult male rgs2^−/− mice (4-8 months) were found to show similar strain-related differences as the aged animals, as well improved glucose clearance and insulin sensitivity, and enhanced beta-adrenergic and glucagon signaling in isolated hepatocytes. In addition, rgs2^−/− pre-adipocytes had reduced levels of differentiation markers (Peroxisome proliferator-activated receptor γ (PPARγ); lipoprotein lipase (Lpl); CCAAT/enhancer binding protein α (CEBPα)) and also rgs2^−/− white adipocytes were small relative to controls, suggesting altered adipogenesis. In wild-type animals, RGS2 mRNA was decreased in brown adipose tissue after cold exposure (7 h at 4 °C) but increased in white adipose tissue in response to a high fat diet, also suggesting a role in lipid storage. No differences between strains were detected with respect to food intake, energy expenditure, GPCR-stimulated lipolysis, or adaptive thermogenesis. In conclusion this study points to RGS2 as being an important regulatory factor in controlling body weight and adipose function.     

Anti-obesity properties of a Sasa quelpaertensis extract in high-fat diet-induced obese mice

This study explores the anti-obesity properties of a Sasa quelpaertensis leaf extract (SQE) in high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. SQE administration with HFD for 70 d significantly decreased the body weight gain, adipose tissue weight, and serum total cholesterol and triglyceride levels in comparison with the HFD group. SQE administration also reduced the serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate dehydrogenase, and the accumulation of lipid droplets in the liver, suggesting a protective effect against HFD-induced hepatic steatosis. SQE administration restored the HFD-induced decreases with phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. SQE also induced AMPK phosphorylation in mature 3T3-L1 adipocytes. These results suggest that SQE exerted an anti-obesity effect on HFD-induced obese mice by activating AMPK in adipose tissue and reducing lipid droplet accumulation in the liver.     

Influence of urea calcium mixture supplementation on ruminal fermentation characteristics of beef cattle fed on concentrates containing high levels of cassava chips and rice straw

The purpose of this study was to evaluate the effects of various N sources in concentrates containing high levels of cassava chips, with rice straw as the basal forage, on rumen ecology, rumen microbial counts, microbial crude (CP) protein synthesis, and digestibility of nutrients. Four ruminally fistulated crossbred (Brahman × native) beef steers with initial body weight (BW) of 400 ± 40.2 kg were randomly assigned according to a 4 × 4 Latin square design. The dietary treatments were different sources of N in the concentrates and were: T1 = urea (control; urea); T2 = soybean meal (SBM); T3 = urea CaCl₂ mixture (U-Cal); T4 = urea CaSO₄ mixture (U-Cas). All steers were kept in individual pens and supplemented with concentrate at 5 g/kg of BW daily. The experiment was 4 periods, and each lasted 21 d. During the first 14 d, all steers were fed their respective diets ad libitum and for during the last 7 d, they were moved to metabolism crates for total urine and fecal collection. Dry matter intake ranged from 9.8 to 10.5 kg daily and was not altered by diet, while digestibility of NDF differed among treatments and was highest with U-Cas supplementation (P<0.05). Ruminal NH₃ N and plasma urea N with U-Cal, U-Cas, and SBM diets were lower compared with the urea supplemented group (P<0.05). Ruminal volatile fatty acid concentrations were not altered by treatments. Total viable, and cellulolytic bacteria, differed among treatments and were highest with U-Cas (9.1 × 10¹¹, and 4.0 × 10⁹ cfu/mL, respectively). In addition, efficiency of rumen microbial CP synthesis based on organic matter (OM) truly digested in the rumen was increased by SBM or U-Cal supplementation, and was highest with U-Cas supplementation (18.2 g of N/kg of OM truly digested in the rumen). Supplementation of U-Cas to a concentrate containing a high level of cassava chips improved rumen ecology and microbial CP synthesis in beef cattle, suggesting that urea calcium mixtures can replace soybean meal or urea in beef cattle diets without adverse affects on rumen fermentation and other rumen parameters.     

The novel gene pFAM134B positively regulates fat deposition in the subcutaneous fat of Sus scrofa

In this study, we analyzed the global gene expression profiles in the subcutaneous fat (SAT) of Jinhua pigs and Landrace pigs at 90 d. Several genes were significantly highly expressed in Jinhua pigs, including genes encoding the rate limiting enzymes in the TCA cycle, fatty acid activation, fatty acid synthesis and triglyceride synthesis. We identified a novel gene tagged by the EST sequences as public No. BF702245.1, which was named porcine FAM134B (pFAM134B) and the pFAM134B mRNA levels of SAT was significantly higher in Jinhua pigs than that in Landrace pigs at 90 d (P < 0.01). Then the effects of pFAM134B on lipid accumulation were investigated by using RNAi and gene overexpression in the subcutaneous adipocytes. The results showed that pFAM134B played a significant positive role in regulating lipid deposition by increasing the mRNA levels of PPARγ, lipogenic genes fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC) (P < 0.01) and reducing the mRNA levels of adipose triglyceride lipase (ATGL) and lipase, hormone-sensitive (HSL) (P < 0.01). This study implied that pFAM134B might be a positive factor in lipid deposition, providing insight into the control of fat accumulation and lipid-related disorders.     

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Lipoic acid (LA) is a naturally occurring compound with beneficial effects on obesity. The aim of this study was to evaluate its effects on lipolysis in 3T3-L1 adipocytes and the mechanisms involved. Our results revealed that LA induced a dose- and time-dependent lipolytic action, which was reversed by pretreatment with the c-Jun N-terminal kinase inhibitor SP600125, the PKA inhibitor H89, and the AMP-activated protein kinase activator AICAR. In contrast, the PI3K/Akt inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and the PDE3B antagonist cilostamide enhanced LA-induced lipolysis. LA treatment for 1 h did not modify total protein content of hormone-sensitive lipase (HSL) but significantly increased the phosphorylation of HSL at Ser⁵⁶³ and at Ser⁶⁶⁰, which was reversed by H89. LA treatment also induced a marked increase in PKA-mediated perilipin phosphorylation. LA did not significantly modify the protein levels of adipose triglyceride lipase or its activator comparative gene identification 58 (CGI-58) and inhibitor G(0)/G(1) switch gene 2 (G0S2). Furthermore, LA caused a significant inhibition of adipose-specific phospholipase A2 (AdPLA) protein and mRNA levels in parallel with a decrease in the amount of prostaglandin E₂ released and an increase in cAMP content. Together, these data suggest that the lipolytic actions of LA are mainly mediated by phosphorylation of HSL through cAMP-mediated activation of protein kinase A probably through the inhibition of AdPLA and prostaglandin E₂.     

Benzafibrate induces acyl-CoA oxidase mRNA levels and fatty acid peroxisomal β-oxidation in rat white adipose tissue

Rats treated with bezafibrate, a PPAR activator, gain less body weight and increase daily food intake. Previously, we have related these changes to a shift of thermogenesis from brown adipose tissue to white adipose tissue attributable to bezafibrate, which induces uncoupling proteins (UCP), UCP-1 and UCP-3, in rat white adipocytes. Nevertheless, UCP induction was weak, implying additional mechanisms in the change of energy homeostasis produced by bezafibrate. Here we show that bezafibrate, in addition to inducing UCPs, modifies energy homeostasis by directly inducing aco gene expression and peroxisomal fatty acid -oxidation in white adipose tissue. Further, bezafibrate significantly reduced plasma triglyceride and leptin concentrations, without modifying the levels of PPAR or ob gene in white adipose tissue. These results indicate that bezafibrate reduces the amount of fatty acids available for triglyceride synthesis in white adipose tissue.