Hormone-sensitive Lipase Expression Research Articles

Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats.

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy.

Bromodomain-containing protein 2 promotes lipolysis via ERK/HSL signalling pathway in white adipose tissue of mice

White adipose tissue (WAT) dysfunction is prevalent among patients with type 2 diabetes mellitus (T2DM). Uncontrolled free fatty acid (FFA) release from WAT stores has detrimental effects on lipid metabolism, leading to insulin resistance. Bromodomain-containing protein 2 (Brd2) has emerged as a central transcriptional regulator of adipocyte differentiation and pancreatic β-cell bioactivity. A recent study shows that Brd2 overexpression leads to insulin resistance in mice. However, the mechanisms underlying these effects have not been fully elucidated. This study provides the first evidence that adenoviral-mediated Brd2 overexpression in the WAT of mice increases lipolysis-related gene expression in addition to significantly reducing WAT size and promoting plasma FFA release. Brd2 overexpression in adipocytes also inhibits fat synthesis-related gene expression, while activating hormone-sensitive lipase (HSL) expression and ERK-dependent perilipin 1 inhibition as well as promoting glycerol release, which are all involved in lipolysis. Collectively, these results indicate that Brd2 triggers insulin resistance via lipolysis-mediated FFA release.

Bariatric Surgery in Rats Upregulates FSP27 Expression in Fat Tissue to Affect Fat Hydrolysis and Metabolism.

Purpose To explore the changes in FSP27 expression and fat metabolism in adipose tissue and their relationship after bariatric surgery in rats. Method Food intake, body weight, triglyceride content, fat distribution, and fat cell morphology were evaluated in rats grouped into control, sham, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) groups. Immunohistochemistry and western blotting were used to detect protein expression and real-time PCR was used to detect mRNA expression. Mouse 3T3-L1 preadipocytes were used to assess the effects of different energy levels and nutrient factors on FSP27 in adipocytes. Result Food intake, body weight, and triglyceride levels were reduced in RYGB and SG rats within 28 days after surgery, with a more pronounced effect in the RYGB group. Weight loss was mainly due to loss of fat mass rather than loss of lean mass, with the most pronounced decrease in trunk fat. FSP27 expression increased in lean rat adipocytes accompanied by increased lipid droplets (LDs). In SG and RYGB rats, the FSP27 protein concentration gradually increased in white adipose tissue (WAT) after operation. Hormone-sensitive lipase (HSL), p-HSL/HSL, Adipose Triglyceride Lipase (ATGL), and Comparative Gene Identification-58 (CGI-58) gradually decreased in SG and RYGB rats, but they were always higher than in control and sham animals. FSP27 was also decreased in 3T3-L1 adipocytes of animals with a high-energy diet. Conclusion FSP27 is associated with rat lipid metabolism and its expression varies with energy and nutrient supply. It can inhibit excessive hydrolysis and fat accumulation by regulating HSL and ATGL expression and by mediating LDs formation.

Vascular endothelial growth factor B inhibits lipid accumulation in C2C12 myotubes incubated with fatty acids

To investigate (1) the effect of vascular endothelial growth factor B (VEGFB) on lipid accumulation and the alteration of fatty acids and fatty acid-related enzymes in C2C12 myotubes incubated with fatty acids and (2) the regulatory effect of VEGFB on skeletal muscle lipid metabolism. Mouse C2C12 myotubes were incubated with oleic acid (OA) and palmitic acid (PA), and differentiated mature C2C12 myotubes were treated with VEGFB. Oil-red O staining, BODIPY staining and cell triglycerides (TG) content were examined. Total RNA was isolated, and real-time PCR analysis was performed. Treatment with 100 μM OA and 50 μM PA induced lipid droplet accumulation and increased TG content (p < .01), and 100 ng/mL VEGFB reduced lipid droplet accumulation and decreased TG content (p < .01). Treatment with 100 ng/mL VEGFB significantly induced the mRNA expression of fatty acid transport protein 1 (FATP1) (p < .01) and FATP4 (p < .01). Treatment with 100 ng/mL VEGFB significantly induced the mRNA expression of adipose TG lipase and hormone-sensitive lipase (p < .01) as well as carnitine palmitoyltransferase I (p < .01), peroxisome proliferator-activated receptor-γ coactivator-1α (p < .01), acyl-coa dehydrogenase very long chain (p < .05), acyl-coa synthetase long-chain family member 1 (p < .01), peroxisomal acyl-coenzyme A oxidase 1 (p < .05), and mitochondrial uncoupling protein 3 (p < .01). VEGFB enhanced FATP1and FATP4 expression, promoted C2C12 myotube fatty acid oxidation and TG decomposition, and inhibited C2C12 myotube fatty acid re-esterification, thus inhibiting lipid accumulation in C2C12 myotubes incubated with fatty acids.

Carbonic anhydrases are involved in mitochondrial biogenesis and control the production of lactate by human Sertoli cells

The process that allows cells to control their pH and bicarbonate levels is essential for ionic and metabolic equilibrium. Carbonic anhydrases (CAs) catalyse the conversion of CO2 to and H+ and are thus essential for this process. Herein, we inhibited CAs with acetazolamide - ACT and SLC-0111 - to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells (hSCs), obtained from biopsies from men with conserved spermatogenesis. We were able to identify three isoforms of CAs, one mitochondrial isoform (CA VB) and two cell membrane-bound isoforms (CA IX and CA XII) in hSCs. When assessing the expression of markers for mitochondrial biogenesis, we observed a decrease in HIF-1α, SIRT1, PGC1α and NRF-1 mRNAs after all CAs were inhibited, resulting in decreased mitochondrial DNA copy numbers. This was followed by an increased production of lactate and alanine in the same conditions. In addition, consumption of glucose was maintained after inhibition of all CAs in hSCs. These results indicate a reduced conversion of pyruvate to acetyl-coA, possibly due to decreased mitochondrial function, caused by CA inhibition in hSCs. Inhibition of CAs also caused alterations in lipid metabolism, since we detected an increased expression of hormone-sensitive lipase (HSL) in hSCs. Our results suggest that CAs are essential for mitochondrial biogenesis, glucose and lipid metabolism in hSCs. This is the first report showing that CAs play an essential role in hSC metabolic dynamics, being involved in mitochondrial biogenesis and controlling lactate production.

Morbid obesity-related changes in the expression of lipid receptors, transporters, and HSL in human sperm.

To study the location and expression of receptors (SR-BI/CLA-1, SR-BII, and LDLr) and transporter (ABCA1) involved in uptake and efflux of cholesterol in human spermatozoa and assess whether obesity alters its location/expression and whether this could be related to infertility. Observational study. None PATIENT(S): Ten controls and 20 obese patients. Anthropometric parameters. Serum and semen samples were collected. Spermatozoon concentration, immunolocalization, and protein expression in semen. Spermatozoon concentration and motility was decreased in morbidly obese patients. SR-BI/CLA-1, SR-BII, LDLr, and ABCA1 are located in the spermatozoon cell membrane and the localization does not change between obese patients and controls. Control spermatozoa showed high SR-BI expression, and less expression for the rest of the receptors analyzed, indicating that SR-BI/CLA-1 is relevant in human spermatozoon cholesterol uptake/efflux. On the contrary, spermatozoa of obese patients showed less SR-BI/CLA-1 expression than controls, and more intense positive staining for SR-BII, LDLr, and ABCA1. Finally, human sperm expresses the 130- and 82-kDa hormone-sensitive lipase (HSL) isoforms. The 130-kDa isoform is expressed in the control sperm, and the expression disappears in the obese patients. The presence of lipid receptors/transporters and HSL in human spermatozoa suggests their role in the process of maturation/capacitation. The changes in the expression of lipid receptors/transporters and the lack of the 130-kDa HSL isoform in obese patients prevent the hydrolysis of cholesterol esters internalized by these receptors, and favor their accumulation in the cytoplasm of the spermatozoa that could contribute to lipotoxicity and infertility.

Regulatory roles of adiponectin receptor 1 and 2 in sheep preadipocytes during adipocyte differentiation

Adipose tissue has long been considered as an energy storage organ. Adipokines, produced by and secreted from adipose tissues, play an important role in regulating fat accumulation, energy balance, and glucose metabolism. Adiponectin receptors (AdipoR1 and AdipoR2) are expressed in various sheep tissues, including adipose tissue. However, the role of adiponectin receptor-mediated signalling has never been investigated in sheep adipose tissue. In this study, sheep preadipocytes were ultimately differentiated into typical adipocytes in vitro 7 days after differentiation. The expression levels of LPL (lipoprotein lipase), HSL (Hormone-sensitive lipase), FAS (fatty acid synthase), and PPARα/PPARγ (peroxisome proliferator-activated receptor alpha/gamma) were significantly changed in the sheep preadipocytes during differentiation for 7 days. After induction of preadipocyte differentiation, lipid accumulation increased significantly in the transfected preadipocytes of AdipoR1-siRNA1 but decreased in the AdipoR1-overexpression (AdipoR1-GFP) preadipocytes. In addition, the expression of HSL and PPARγ was significantly changed in preadipocytes by transfected with AdipoR1-siRNA1 or AdipoR1-GFP. However, the lipid accumulation and adipogenic gene expression were not significantly changed in preadipocytes by transfected with AdipoR2-siRNA2 and AdipoR2-GFP. Taken together, these results indicate that AdipoR1 could regulate sheep adipose metabolism via regulating HSL and PPARγ expression during adipocyte differentiation.HighlightsWe first established an in vitro culture system for sheep preadipocytes derived from the paraspinal muscle adipose.Sheep preadipocytes were ultimately differentiated into typical adipocytes after induction and differentiation.Both suppression and overexpression of adiponectin receptor 1 expression affect lipid accumulation and adipocyte metabolism during adipocyte differentiation.

Sex Differences in Inflammatory Responses to Adipose Tissue Lipolysis in Diet-Induced Obesity.

Males are known to have profound adipose tissue macrophage (ATM) accumulation in gonadal white adipose tissue (GWAT) during obesity, whereas females are protected from such an inflammatory response even with increased adiposity. The inflammatory tone in males is linked to insulin resistance and might be the underlying cause for sex differences in metabolic disease. Factors regulating the meta-inflammatory response remain unclear but enhanced lipid storage in females may explain the reduced inflammatory response to high-fat diets. In this study, we evaluated lean and obese females with stimulated lipolysis to understand whether a stress release of free fatty acids (FFAs) could induce female ATMs. We demonstrate that in both lean and obese females, GWAT CD11c- resident ATMs accumulate with β-3 adrenergic receptor-stimulated lipolysis. Lipolysis elevated serum FFA, triglyceride, and IL-6 levels in females that corresponded to significant phosphorylated hormone-sensitive lipase and adipose triglyceride lipase protein expression in obese female GWAT compared with males. Increased lipolytic response in obese females was associated with crown-like structures and induced Il6, Mcp1, Arg1, and Mgl1 expression in obese female GWAT, suggesting an environment of lipid clearance and adipose remodeling. With this finding we next investigated whether lipid storage and lipolytic mediators differed by sex. Diacylglycerol, ceramides, phospholipids, and certain fatty acid species associated with inflammation were elevated in male GWAT compared with obese female GWAT. Overall, our data demonstrate a role for GWAT lipid storage and lipolytic metabolites to induce inflammation in males and induce remodeling in females that might explain sex differences in overall metabolic health.

Effects of fish oil with difference oxidation degree on growth performance and expression abundance of antioxidant and fat metabolism genes in orange spotted grouper,Epinephelus coioides

The present study was designed to assess the effects of fish oil with different oxidation degree on growth performance, serum biochemistry parameters and expressive abundance of oxidative stress and fat metabolism genes of orange spotted grouper Epinephelus coioides. The oxidized fish oil was conducted as follows: storage temperature: 4°C, ambient temperature (AT, [31.5 ± 3.5]°C); storage time: 45, 90, 135 days; antioxidant contents: 30 mg/kg (ethoxyquin [EQ]), 300 mg/kg Higher EQ (HEQ). According to the different treated conditions, 14 kinds of fish oil with different oxidation degree were obtained: TF+EQ [positive control (fresh oil + EQ)], TF (negative control [fresh oil]), T4°C+45d+EQ, T4°C+45d+HEQ, T4°C+90d+EQ, T4°C+90d+HEQ, T4°C+135d+EQ, T4°C+135d+HEQ, TAT+45d+EQ, TAT+45d+HEQ, TAT+90d+EQ, TAT+90d+HEQ, TAT+135d+EQ, TAT+135d+HEQ. Groupers were fed isonitrogenous and isolipidic diets containing 14 kinds of fish oil for 8 weeks, respectively. The results showed that survival, weight gain rate and thermal growth coefficient decreased as oxidation degree of dietary fish oil increased (p < 0.05). Higher serum total protein, triglyceride and glucose were observed with ascending oxidation degree of fish oil (p < 0.05). The genes expression levels of catalase, superoxide dismutase and glutathione peroxidase were up-regulated with dietary oxidized level increasing (p < 0.05). In addition, the similar status also appeared in expression of peroxisome proliferator-activated receptor gamma (PPARγ), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) genes. In conclusion, the fish oil would show negative influence on the fish health until peroxide value and p-anisidine value in oil exceed 12.96 meq/kg and 20.89. The best storage condition for fish oil is 4°C, 45 days and 30 mg/kg EQ which could keep fish oil available property to grouper.

MicroRNA-128 is involved in dexamethasone-induced lipid accumulation via repressing SIRT1 expression in cultured pig preadipocytes

In this study, pig preadipocytes were firstly treated with 10−6 M DEX for 48 h to explore the role of dexamethasone (DEX, a chemically synthesized long-acting glucocorticoid) on lipid accumulation. Then, miRNA scrambled control (miR-SC), miR-128 overexpression plasmid and miR-128 inhibitor were respectively transfected into pig preadipocytes at 24 h before DEX treatment for 48 h (miR-SC-DEX, miR-128-DEX and miR-128-inhibitor-DEX) to illustrate the regulatory role of miR-128 on DEX-induced lipid accumulation. Compared with control preadipocytes, 10-6 M Dex significantly increased triglyceride (TG) level, whereas the cell proliferation did not change. Moreover, 10-6 M Dex obviously decreased sirtuin 1 (SIRT1) and its related lipolysis genes adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) mRNA expression and enzyme activity, while significantly increased expression of adipogenesis genes peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α (C/EBP-α) and fatty acid synthase (FAS). In addition, 10-6 M DEX significantly upregulated miR-128 expression, which was confirmed to directly target SIRT1 by bioinformatics analysis and dual-luciferase reporter assay. Gain- and loss-of-function study also showed that when compared with miR-SC-DEX cells, miR-128-DEX cells showed significantly reduced SIRT1 expression and increased TG level, as well as elevated cellular levels of PPAR-γ, C/EBP-α and FAS and suppressed ATGL and HSL expression and enzyme activity. In contrast, miR-128-inhibitor-DEX cells precisely presented the opposite results. Collectively, these results indicate that miR-128 plays a role in the pathogenesis of glucocorticoid-related abnormal lipid accumulation via repressing SIRT1 expression, consequently, miR-128 inhibition may represent a novel potential therapeutic target in preventing DEX-induced abnormal lipid accumulation.

Effects of capsicoside G isolated from pepper seeds on lipolysis and fatty acid oxidation‐related gene expression in 3T3‐L1 adipocytes

We previously demonstrated that capsicoside G, a furostanol saponin isolated from pepper seeds, inhibits adipogenesis in 3T3-L1 adipocytes. However, the effects of capsicoside G on lipolysis and fatty acid oxidation remain unclear. The purpose of this study was to extend the anti-obesity investigation of capsicoside G by examining its effect on lipolysis and fatty acid oxidation-related gene expression in mature 3T3-L1 adipocytes. Capsicoside G promoted lipolysis of adipocytes, which effectively decreased the intracellular triglyceride concentration of adipocytes and increased the amount of glycerol released into the medium. Increased lipolysis was accompanied by augmented expression of adipose triglyceride lipase and hormone-sensitive lipase. Furthermore, capsicoside G induced the expression of fatty acid oxidative genes such as peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1 in mature 3T3-L1 adipocytes. These results suggest that capsicoside G exerts anti-obesity effects by stimulating lipolysis and fatty acid oxidation-related gene expression in mature 3T3-L1 adipocytes. Practical application Capsicoside G, a furostanol saponin isolated from pepper seeds, has been reported to have inhibitory effects on lipid accumulation and adipogenesis by activating AMP-activated protein kinase in 3T3-L1 cells, thus suggesting their anti-obesity potential. In this study, capsicoside G stimulated lipolysis and fatty acid oxidation-related gene expression in mature 3T3-L1 adipocytes. Therefore, our findings suggest that capsicoside G is a promising therapeutic tool for obesity and obesity-related metabolic syndromes.

Potential Crosstalk between Fructose and Melatonin: A New Role of Melatonin-Inhibiting the Metabolic Effects of Fructose.

Increased consumption of energy-dense foods such as fructose-rich syrups represents one of the significant, growing concerns related to the alarming trend of overweight, obesity, and metabolic disorders worldwide. Metabolic pathways affected by fructose involve genes related to lipogenesis/lipolysis, beta-oxidation, mitochondrial biogenesis, gluconeogenesis, oxidative phosphorylation pathways, or altering of circadian production of insulin and leptin. Moreover, fructose can be a risk factor during pregnancy elevating the risk of preterm delivery, hypertension, and metabolic impairment of the mother and fetus. Melatonin is a chronobiotic and homeostatic hormone that can modulate the harmful effects of fructose via clock gene expression and metabolic pathways, modulating the expression of PPARγ, SREBF-1 (SREBP-1), hormone-sensitive lipase, C/EBP-α genes, NRF-1, PGC1α, and uncoupling protein-1. Moreover, this hormone has the capacity in the rat of reverting the harmful effects of fructose, increasing the body weight and weight ratio of the liver, and increasing the body weight and restoring the glycemia from mothers exposed to fructose. The aim of this review is to show the potential crosstalk between fructose and melatonin and their potential role during pregnancy.

Effects of starvation on glucose and lipid metabolism in gibel carp (Carassius auratus gibelio var. CAS III)

Many fish species experience natural periods of starvation; however, mobilization of energy sources may vary. To elucidate the mechanism underlying energy utilization and metabolic adaptation to food deprivation in gibel carp (Carassis auratus gibelio var. CAS III), fish (initial body weight: 111.13 ± 0.65 g) were starved for 0 d, 1 d, 2 d, 7 d, and 21 d, respectively. After seven days of food deprivation, plasma glucose levels significantly decreased, whereas plasma free fatty acids levels significantly increased. Liver glycogen levels in the group starved for 7 d significantly decreased, whereas muscle glycogen levels decreased in the group starved for 21 d, suggesting that glycogen in the liver is first utilized to provide energy than glycogen in the muscle. The transcriptional levels of glucose transporter type 2 (GLUT2) in the liver were upregulated during starvation. No changes in the mRNA levels of glycolytic enzymes such as glucokinase (GK) and 6-phosphofructokinase (6PFK) were observed in the liver. Gluconeogenic potential increased with starvation, possibly for blood glucose homeostasis, as indicated by the enhanced mRNA levels of gluconeogenic enzymes, including glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase), and phosphoenolpyruvate carboxykinase (PEPCK). The observation of a decrease in liver triglycerides content and the enhanced expression of hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) suggests the mobilization of lipid reserve in the liver. Enhanced fatty acid oxidation as indicated by the upregulated mRNA carnitine palmitoyl transferase 1 isoform a (CPT1a) and acyl-CoA oxidase 3 (ACO3) levels in the liver suggests that fatty acids are catabolized to provide energy during starvation. Sterol regulatory element binding protein 1 (SREBP1), ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) were downregulated during starvation in both liver and muscle, indicating suppressed lipogenesis.

Expression of ApoE Attenuates Differentiation of the White Adipose Tissue from ApoE-Knockout Diabetic Mice

Background: What and how the adipose-derived ApoE regulates biological features and lipid metabolism in the diabetic adipose tissue remain little known. Methods: ApoE-/- and wild type mice were randomly divided into 4 groups: ApoE-/- group (EKO); streptozotocin (STZ)-induced diabetic apoE-/- group (EKODM); wild type group(WT); and STZ-induced diabetic wild type group (WTDM). Epididymal white adipose tissue isolated from part EKODM mice were transplanted into backs of WT mice and WTDM mice respectively, all recipient mice were fed with standard chow for 8 weeks. Vital signs, fasting plasma glucose, serum triglycerides(TG) and total cholesterol(TC) were measured every 4 weeks. After sacrifice, epididymal and transplanted white adipose tissue were harvested from all recipient mice. Histomorphologic alterations of adipose tissue were observed. Lipid ingredients of adipose tissue were extracted and measured. Genes expression of ApoE,lipoprotein lipase (LPL),hormone sensitive lipase(HSL),fatty acid synthase(FAS) in adipose tissue were detected by the RT-PCR. Results: 1) After transplantation, the donor adipocytes size from EKODM→WT and EKODM→WTDM mice were both larger than that of EKODM itself. 2) Adipose TG contents of EKO and WTDM group were both lower than that of WT group, while EKODM→WT transplantation increased TG content but kept TC content unchanged compared with the EKODM→WTDM. 3) Adipose tissues of EKODM→WT and EKODM→WTDM group both significantly expressed ApoE. 4) Gene expressions of HSL, LPL, and FAS in donor adipose tissues from either EKODM→WT and EKODM→WTDM group were all significantly increased if compared with the EKODM group. Conclusions: Adipose-derived ApoE may facilitate adipocyte differentiation in mice, even in a diabetic state. Disclosure J. Ran: None. X. Pan: None. R. Zhang: None. P. Zhu: None. R. Tan: None. Y. Liu: None.

Effects of phytonutrients alone or in combination with monensin on productivity in lactating dairy cows

This experiment was conducted to investigate the effects of phytonutrients, compared with monensin as a positive control, on productivity, milk fatty acids, fat mobilization, and blood cells in lactating dairy cows. Thirty-six Holstein cows were used in a 9-wk randomized complete block design study. Following a 2-wk covariate period, cows were blocked by days in milk, parity, and milk yield and randomly assigned to 1 of 3 treatments (12 cows/treatment): 450 mg/cow per day of monensin (MO), 250 mg/cow per day of capsicum plus 450 mg/cow per day of MO (MOCAP), and 1,000 mg/cow per day of a mixture of cinnamaldehyde, eugenol, and capsicum (CEC). Dry matter intake and milk yield were not affected by treatment. Supplementation of CEC increased feed efficiency compared with MO, but did not affect feed efficiency on an energy-corrected milk basis. Milk composition (fat, protein, and lactose), milk fatty acid profile, and blood concentrations of nonesterified fatty acids and β-hydroxybutyrate were also not affected by treatment. The expression of hormone-sensitive lipase in adipose tissues tended to increase for MOCAP compared with MO. Counts of total white blood cell, neutrophils, lymphocytes, eosinophils, and basophils were not affected by treatment, although monocytes count tended to be decreased by CEC. Treatments had no effect on red blood cells, hemoglobin, and platelets. Results indicate that dietary supplementation of CEC and capsicum had no production or other effects in dairy cows, compared with MO, except CEC increased feed efficiency and tended to decrease blood monocytes count.

Downregulated angiopoietin-like protein 8 production at calving related to changes in lipid metabolism in dairy cows.

Acute physiological adaptation of lipid metabolism during the postpartum transition period of cows facilitates peripheral metabolic regulation. Hepatokines, which are hormones secreted from hepatocytes, are presumed to play a critical role in systemic metabolic regulation. Angiopoietin-like protein 8 (ANGPTL8) has been identified as a novel hepatokine associated with circulating triglyceride concentrations in mice and humans. However, regulation of ANGPTL8 and its physiological effects is still unknown in cattle. The present study aimed to reveal changes in ANGPTL8 expression and secretion during the periparturient period, and to investigate its regulatory effect on adipocytes and mammary epithelial cells. In the peripartum period, liver ANGPTL8 mRNA expression was lesser on the day of parturition and 1 wk postpartum than it was 1 wk before parturition (P < 0.05). Moreover, plasma ANGPTL8 concentrations decreased on the day of parturition as compared with that 1 wk before parturition (P < 0.05). In addition, ANGPTL8 expression in cultured bovine hepatocytes was downregulated after oleate and palmitate treatment but upregulated after insulin treatment (P < 0.05). ANGPTL8 decreased hormone-sensitive lipase (HSL) expression in differentiated adipocytes and cluster of differentiation 36 (CD36), fatty acid synthase (FAS), acetyl-coa carboxylase (ACC), and stearoyl-coa desaturase (SCD) in cultured bovine mammary epithelial cells (P < 0.05). These data suggest that hepatic ANGPTL8 production was downregulated postpartum when the cows experienced a negative energy balance. This downregulation was associated with increased concentrations of NEFA and decreased concentrations of insulin in lactating cows, and it facilitated lipid mobilization from adipose tissue to the mammary glands. We speculate that ANGPTL8 might have beneficial effects in reverting or improving the physiological adaptation and pathological processes of lipid metabolism during the peripartum period.

Functional interplay between liver X receptor and AMP-activated protein kinase α inhibits atherosclerosis in apolipoprotein E-deficient mice - a new anti-atherogenic strategy.

The liver X receptor (LXR) agonist T317 reduces atherosclerosis but induces fatty liver. Metformin activates energy metabolism by activating AMPKα. In this study, we determined if interactions between metformin and T317 could inhibit atherosclerosis without activation of hepatic lipogenesis. Apolipoprotein E-deficient mice were treated with T317, metformin or both agents, in a high-fat diet for 16weeks. Then, samples of aorta, liver, macrophage and serum were collected to determine atherosclerotic lesions, fatty liver, lipid profiles and expression of related proteins. Techniques used included immunohistochemistry, histology, qRT-PCR and Western blot. T317 inhibited en face and aortic root sinus lesions, and the inhibition was further enhanced by addition of metformin. Co-treatment with metformin and T317 increased lesion stability, by increasing collagen content, and reducing necrotic cores and calcification. Formation of macrophages/foam cells and their accumulation in arterial wall were inhibited by the co-treatment, which was accompanied by increased ABCA1/ABCG1 expression, reduced monocyte adhesion and apparent local proliferation of macrophages. Metformin blocked T317-induced fatty liver by inhibiting T317-induced hepatic LXRα nuclear translocation and expression of lipogenic genes and by activating AMPKα. Moreover, co-treatment with T317 and metformin improved triglyceride metabolism by inducing expression of adipose triglyceride lipase, hormone-sensitive lipase, PPARα and carnitine acetyltransferase and by inhibiting acyl-CoA:diacylglycerol acyltransferase 1 expression. Co-treatment with T317 and metformin inhibited the development of atherosclerosis without activation of lipogenesis, suggesting that combined treatment with T317 and metformin may be a novel approach to inhibition of atherosclerosis.

Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

Differential response of adipose tissue gene and protein expressions to 4- and 8-week administration of β-guanidinopropionic acid in mice.

β‐Guanidinopropionic acid (β‐GPA) feeding inhibits growth‐associated gain of body mass. It remains unknown, however, whether and how β‐GPA feeding affects growth‐associated increase in white adipose tissue (WAT) mass. We examined the effects of 4‐ and 8‐week β‐GPA feeding on serum myostatin levels and expression of genes and proteins related to adipogenesis, lipolysis, and liposynthesis in epididymal WAT (eWAT) and brown adipose tissue (BAT) in 3‐week‐old, juvenile male mice. Body, eWAT, and muscle weights were significantly lower in β‐GPA‐fed mice than in controls after feeding. Four‐ but not 8‐week‐β‐GPA feeding increased the serum myostatin level. Incubation of C2C12 myotubes with β‐GPA (1 mM) significantly promoted myostatin mRNA expression. The protein expression of peroxisome proliferator‐activated receptor gamma coactivator 1 α (PGC‐1α) and peroxisome proliferator‐activated receptor α (PPAR α) was up‐regulated in GPAF eWAT at week 4, but down‐regulated at week 8. There was no significant difference in the protein expression of adipocyte triglyceride lipase (ATGL), hormone‐sensitive lipase (HSL), fatty acid synthase (FAS), and acetyl‐CoA carboxylase (ACC) between groups in eWAT. In BAT, no significant difference was found in the protein expression of PGC‐1α, PPAR α, ATGL, and HSL between β‐GPA‐fed and control mice, whereas that of FAS and ACC was significantly lower in β‐GPA‐fed mice at week 8. Uncoupling protein 1 was expressed higher in β‐GPA‐fed mice both at weeks 4 and 8 than that in controls. Thus, the mechanism by which β‐GPA feeding in early juvenile mice inhibits growth‐associated increase in eWAT mass may differ between early and later periods of growth.

Genipin ameliorates diet-induced obesity via promoting lipid mobilization and browning of white adipose tissue in rats.

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and β-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.