Hormone-sensitive Triglyceride Lipase Research Articles

Dietary phosphorus requirement of bullfrog Lithobates (Aquarana) catesbeiana

This experiment investigated the dietary phosphorus (P) requirement of bullfrogs Lithobates (Aquarana) catesbeiana. Six diets containing available P (AP) levels of 0.29% (the control group), 0.47%, 0.65%, 0.88%, 1.06% and 1.24% were formulated and fed to bullfrogs for 56 days. As the dietary AP level increased from 0.29% to 1.24%, the weight gain rate increased and then decreased, reaching the highest at the AP level of 0.88% (P < 0.05). Compared to the control group, content of crude protein in the whole-body was significantly increased in bullfrogs fed the 0.88% AP diet (P < 0.05). Content of crude lipid in the whole-body was significantly decreased in bullfrogs fed the 0.65%, 0.88%, 1.06% and 1.24% AP diets compared to those fed the 0.29% and 0.47% AP diets (P < 0.05). Bullfrogs fed the 0.65%, 0.88%, 1.06%, and 1.24% AP diets had higher content of serum P than those fed the 0.29% and 0.47% AP diets (P < 0.05). Activity of glutamic pyruvic transaminase in the serum was significantly decreased in bullfrogs fed the 0.88%, 1.06% and 1.24% AP diets compared to those fed the 0.29% and 0.47% AP diets (P < 0.05). Bullfrogs fed the 0.65%, 0.88%, 1.06% and 1.24% AP diets had lower contents of total cholesterol in the liver and triglycerides in the serum than the control group (P < 0.05). Meanwhile, bullfrogs fed the 0.47%, 0.65%, 0.88% and 1.06% AP diets had higher total antioxidant capacity in the serum than the control group (P < 0.05). Compared to the control group, contents of P and calcium in the whole-body were significantly increased in bullfrogs fed the 0.65%, 0.88%, 1.06% and 1.24% AP diets (P < 0.05). Compared to the control group, bullfrogs fed the 0.88%, 1.06% and 1.24% AP diets had lower expression of sodium-dependent phosphate transporter in the intestine and kidney, and higher expression of hormone-sensitive triglyceride lipase in the liver (P < 0.05). Bullfrogs fed the 0.88% and 1.06% AP diets had higher the mucosal fold height than those fed the 0.29% and 1.24% AP diets (P < 0.05). Compared to those fed the 0.29% and 1.24% AP diets, the abundance of potentially pathogenic bacteria Serratia and Acinetobacter in the intestine was decreased in bullfrogs fed the 0.88% AP diet. Using the weight gain rate, feed efficiency, whole-body and serum P content as evaluation indicators, the AP requirements of bullfrogs was 0.82% to 0.89%.

Mulberry Leaf Dietary Supplementation Can Improve the Lipo-Nutritional Quality of Pork and Regulate Gut Microbiota in Pigs: A Comprehensive Multi-Omics Analysis.

Mulberry leaves, a common traditional Chinese medicine, represent a potential nutritional strategy to improve the fat profile, also known as the lipo-nutrition, of pork. However, the effects of mulberry leaves on pork lipo-nutrition and the microorganisms and metabolites in the porcine gut remain unclear. In this study, multi-omics analysis was employed in a Yuxi black pig animal model to explore the possible regulatory mechanism of mulberry leaves on pork quality. Sixty Yuxi black pigs were divided into two groups: the control group (n = 15) was fed a standard diet, and the experimental group (n = 45) was fed a diet supplemented with 8% mulberry leaves. Experiments were performed in three replicates (n = 15 per replicate); the two diets were ensured to be nutritionally balanced, and the feeding period was 120 days. The results showed that pigs receiving the diet supplemented with mulberry leaves had significantly reduced backfat thickness (p < 0.05) and increased intramuscular fat (IMF) content (p < 0.05) compared with pigs receiving the standard diet. Lipidomics analysis showed that mulberry leaves improved the lipid profile composition and increased the proportion of triglycerides (TGs). Interestingly, the IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, the cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG-005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, and Limosilactobacillus. Simultaneously, the relative levels of L-tyrosine-ethyl ester, oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, and mulberrin were increased. Furthermore, we found that mulberry leaf supplementation significantly increased the mRNA expression of lipoprotein lipase, fatty acid-binding protein 4, and peroxisome proliferators-activated receptor γ in muscle (p < 0.01). Mulberry leaf supplementation significantly increased the mRNA expression of diacylglycerol acyltransferase 1 (p < 0.05) while significantly decreasing the expression of acetyl CoA carboxylase in backfat (p < 0.05). Furthermore, mulberry leaf supplementation significantly upregulated the mRNA expression of hormone-sensitive triglyceride lipase and peroxisome proliferator-activated receptor α (p < 0.05) in backfat. In addition, mulberry leaf supplementation led to increased serum leptin and adiponectin (p < 0.01). Collectively, this omic profile is consistent with an increased ratio of IMF to backfat in the pig model.

Role of diacylglycerol O-acyltransferase 1 (DGAT1) in lipolysis and autophagy of adipose tissue from ketotic dairy cows

High-yielding dairy cows in early lactation often encounter difficulties in meeting the energy requirements essential for maintaining milk production. This is primarily attributed to insufficient dry matter intake, which consequently leads to sustained lipolysis of adipose tissue. Fatty acids released by lipolysis can disrupt metabolic homeostasis. Autophagy, an adaptive response to intracellular environmental changes, is considered a crucial mechanism for regulating lipid metabolism and maintaining a proper cellular energy status. Despite its close relationship with aberrant lipid metabolism and cyto-lipotoxicity in animal models of metabolic disorders, the precise function of diacylglycerol o-acyltransferase 1 (DGAT1) in bovine adipose tissue during periods of negative energy balance (NEB) is not fully understood. Particularly regarding its involvement in lipolysis and autophagy. The objective of the present study was to assess the impact of DGAT1 on both lipolysis and autophagy in bovine adipose tissue and isolated adipocytes. Adipose tissue and blood samples were collected from cows diagnosed as clinically ketotic (n = 15) or healthy (n = 15) following a veterinary evaluation based on clinical symptoms and serum concentrations of BHB, which were 3.19 mM (interquartile range = 0.20) and 0.50 mM (interquartile range = 0.06), respectively. Protein abundance of DGAT1 and phosphorylation levels of unc-51-like kinase 1 (ULK1), were greater in adipose tissue from cows with ketosis, whereas phosphorylation levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were lower. Furthermore, when adipocytes isolated from the harvested adipose tissue of 15 healthy cows were transfected with DGAT1 overexpression adenovirus or DGAT1 small interfering RNA followed by exposure to epinephrine (EPI), it led to greater ratios and protein abundance of phosphorylated hormone-sensitive triglyceride lipase (LIPE) to total LIPE and adipose triglyceride lipase (ATGL), while inhibiting the protein phosphorylation levels of ULK1, PI3K, AKT and mTOR. Overexpression of DGAT1 in EPI-treated adipocytes reduced lipolysis and autophagy, whereas silencing DGAT1 further exacerbated EPI-induced lipolysis and autophagy. Taken together, these findings indicate that upregulation of DGAT1 may function as an adaptive response to suppress adipocytes lipolysis, highlighting the significance of maintaining metabolic homeostasis in dairy cows during periods of NEB.

Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells.

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.

How Do Different Dietary Carbohydrate/Lipid Ratios Influence Intestinal Morphology and Glycolipid Metabolism Capacity in Hybrid Grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂)

Levels of dietary carbohydrates and lipids have important effects on the growth, health, and glycolipid metabolizing capacity of the hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). This experiment evaluated the effect of carbohydrate to lipid ratios (CHO:L ratio) on growth, serum biochemical indices, intestinal morphology and activity of digestive enzymes, and the ability to metabolize carbohydrates and lipids in the hybrid grouper. Six iso-nitrogenous (500 g/kg) and iso-energetic (190 MJ/kg) feeds with CHO:L ratios of 0.82, 1.03, 1.28, 1.58, 1.94, and 2.27 were formulated. The 720 groupers with an initial body weight of 7.76 ± 0.08 g were sorted into 24 fiberglass buckets of 30 fish each. Feed was delivered twice daily at 8:00 and 16:00 to apparent satiety for 56 days. The results showed that the growth performance of the groupers was not significantly affected by the diet. Based on the specific growth rate (SGR), the optimal CHO:L ratio was 1.72 for the groupers by the second-order polynomial regression model. The intestinal trypsin and lipase, and the hepatic trypsin activities of the groupers showed a maximum in the 1.58 group. The intestinal muscle thickness in the 1.94 group and the villus length in the 1.58 group were significantly greater than in the 0.82, 1.03, 1.28, and 2.27 groups. The glycogen synthase, pyruvate kinase, and hexokinase activities of the liver were significantly higher in the 1.58 group than in the 0.82 and 2.27 groups. The hormone-sensitive triglyceride lipase, adipose triglyceride lipase, acetyl-CoA carboxylase, and carnitine palmitoyl transferase of the liver showed significantly higher activities in the 1.58 group than those in the 0.82 and 1.03 groups. These results showed that based on the SGR of the groupers, the best CHO:L ratio was 1.72. An appropriate dietary CHO:L ratio can reduce the lipid deposition of the fish body, liver, and muscle, as well as improve the intestinal morphology and activities of liver carbohydrate and lipid metabolism enzymes.

N-carbamoyl aspartate reduced body weight by stimulating the thermogenesis of iBAT

Uridine has formerly been shown to alleviate obesity and hepatic lipid accumulation. N-carbamoyl aspartate (NCA) provides carbon atoms to uridine in de novo pyrimidine biosynthesis pathway. However, whether NCA is involved in the lipid metabolism remains elusive. Here we showed that NCA supplementation significantly decreased (P < 0.05) serum cholesterol (CHOL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels of mice, and significantly increased (P < 0.05) relative mRNA expression of genes related to the synthesis of pyrimidine nucleotides and polyunsaturated fatty acids. Besides, supplemented with NCA significantly decreased body weight and area under the curve (AUC), and increased body temperature in the high-fat diet fed mice. For further, relative protein expression of uridine monophosphate synthase (UMPS), sterol regulatory element-binding protein 1(SREBP-1) and phosphorylated hormone-sensitive triglyceride lipase (P-HSL) in the liver, and uncoupling protein 1 (UCP-1) in interscapular brown adipose tissue (iBAT) also showed upregulated in the high-fat diet fed mice. Thus, NCA promoted de novo synthesis of pyrimidine and polyunsaturated fatty acid, and reduced body weight by stimulating high-fat diet-induced thermogenesis of iBAT.

Branched-chain amino acid modulation of lipid metabolism, gluconeogenesis, and inflammation in a finishing pig model: targeting leucine and valine.

Branched-chain amino acids (BCAAs) play a regulatory role in adipogenesis and energy balance. Therefore, this study aimed to investigate the impact of BCAA supplements, especially leucine (Leu) and valine (Val) supplementation, on lipid metabolism and related disorders in a finishing pig model. The results demonstrated that Leu (1%) and Val decreased serum as well as hepatic lipid accumulation. Moreover, metabolomics and lipidomics analyses revealed that Leu and Val markedly downregulated the level of various lipid species in the liver. This outcome may be explained by Leu and Val promoting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathways. Leu and Val altered the fatty acid composition in distinct adipose tissues and decreased the levels of inflammatory factors. Additionally, they significantly decreased back fat thickness, and the results of the fatty acid profiles demonstrated that Leu and Val significantly increased the levels of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) while decreasing those of saturated fatty acids (SFAs), especially in back fat and abdominal fat. Besides, Leu and Val restored glucose homeostasis by suppressing gluconeogenesis through the serine/threonine protein kinase (AKT)/transcription factor forkhead box O1 (FOXO1) signaling pathway in the liver and back fat. In summary, these results suggest that Leu and Val may serve as key regulators for modulating lipid metabolism and steatosis.

Ramulus Mori (Sangzhi) Alkaloids Ameliorate Obesity-Linked Adipose Tissue Metabolism and Inflammation in Mice

Obesity has become a global epidemic disease as it is closely associated with a chronic low-grade inflammatory state that results in metabolic dysfunction. Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from Morus alba L. were licensed to treat type 2 diabetes (T2DM) in 2020. In this study, we explored the effect of SZ-A on adipose tissue metabolism and inflammation using an obesity model induced by a high-fat diet (HFD). C57BL/6J mice were fed high fat for 14 weeks and followed by SZ-A 400 mg/kg treatment via gavage for another six weeks, during which they were still given the high-fat diet. The results showed that SZ-A notably reduced body weight and serum levels of lipid metabolism-related factors, such as triglycerides (TG) and total cholesterol (TC); and inflammation-related factors, namely tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), fibrinogen activator inhibitor-1 (PAI-1), angiopoietin-2 (Ang-2), and leptin (LEP), in the HFD-induced mice. SZ-A increased the protein and mRNA expression of lipid metabolism-related factors, including phosphorylated acetyl coenzyme A carboxylase (p-ACC), phosphorylated hormone-sensitive triglyceride lipase (p-HSL), adipose triglyceride lipase (ATGL), and peroxisome proliferator-activated receptor-alpha (PPARα), in adipose tissue. Immunohistochemistry results demonstrated that SZ-A significantly reduced the infiltration of pro-inflammatory M1-type macrophages in epididymal fat. The data also suggested that SZ-A down-regulates the transcriptional levels of inflammatory factors Il6, Tnfα, monocyte chemoattractant protein-1 (Mcp1), and F4/80, and up-regulates interleukin 4 (Il4), interleukin 10 (Il10), and interleukin 13 (Il13) in adipose tissue. Overall, the results indicate that SZ-A exhibits potential in regulating lipid metabolism and ameliorating obesity-linked adipose inflammation.

Si–Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation

Ethnopharmacological relevanceSi–Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated.Aim of the study: This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. Materials and methodsThe high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. ResultsOur results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. ConclusionThe results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.

Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats.

Diabetes is a disease that is characterized by a disturbance of glucose metabolism. Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. Diabetic GK rats were treated up to 8 weeks with TB (GK-TB). Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. The Firmicutes/Bacteroides ratio was decreased significantly, and the composition of Actinobacteria and Proteobacteria was increased. The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). PD significantly reduced serum LDL, while the effect of LM was not significant. However, LM and PD significantly increased the content of ADPN in serum. Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes.

A Study on How Methionine Restriction Decreases the Body's Hepatic and Lipid Deposition in Rice Field Eel (Monopterus albus).

Methionine restriction reduces animal lipid deposition. However, the molecular mechanism underlying how the body reacts to the condition and regulates lipid metabolism remains unknown. In this study, a feeding trial was performed on rice field eel Monopterus albus with six isonitrogenous and isoenergetic feeds that included different levels of methionine (0, 2, 4, 6, 8, and 10 g/kg). Compared with M0 (0 g/kg), the crude lipid and crude protein of M. albus increased markedly in M8 (8 g/kg) (p < 0.05), serum (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and non-esterified free fatty acids), and hepatic contents (hepatic lipase, apolipoprotein-A, fatty acid synthetase, total cholesterol, triglyceride, and lipoprteinlipase). However, in the serum, very-low-density lipoprotein and hepatic contents (hormone-sensitive triglyceride lipase, Acetyl CoA carboxylase, carnitine palmitoyltransterase, and mirosomal triglygeride transfer protein) decreased markedly in M8 (p < 0.05). The contents of hepatic C18:2n-6, C22:6n-3, and n-3PUFA in the M8 group were significantly higher than those in M0 (p < 0.05), and the contents of lipid droplets in M8 were higher than those in M0. Compared with M0, the hepatic gcn2, eif2α, hsl, mttp, ldlrap, pparα, cpt1, and cpt2 were remarkably downregulated in M8, while srebf2, lpl, moat2, dgat2, hdlbp, srebf1, fas, fads2, me1, pfae, and icdh were markedly upregulated in M8. Moreover, hepatic SREBP1 and FAS protein expression were upregulated significantly in M8 (p < 0.01). In short, methionine restriction decreased the lipid deposition of M. albus, especially for hepatic lipid deposition, and mainly downregulated hepatic fatty acid metabolism. Besides, gcn2 could be activated under methionine restriction.

The Effects of Erchen Decoction on Gut Microbiota and Lipid Metabolism Disorders in Zucker Diabetic Fatty Rats.

Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.

Impact of Dietary Crude Protein Level on Hepatic Lipid Metabolism in Weaned Female Piglets.

Simple SummaryIt has been reported that a high crude protein diet could reverse the diet-induced lipid accumulation in the liver of mice and rodents. However, in vivo data supporting a functional role of a high crude protein diet on hepatic lipid metabolism-associated genes and proteins in weaned piglets is not available. In the present study, we aimed to provide a mechanistic insight into alterations in the hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis in response to different dietary crude protein levels. Our results demonstrated that dietary crude protein could regulate hepatic lipid metabolism through regulating hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis. The result indicated an important role of dietary crude protein in regulating hepatic lipid metabolism in weaned piglets.Amino acids serve not only as building blocks for proteins, but also as substrates for the synthesis of low-molecular-weight substances involved in hepatic lipid metabolism. In the present study, eighteen weaned female piglets at 35 days of age were fed a corn- and soybean meal-based diet containing 20%, 17%, or 14% crude protein (CP), respectively. We found that 17% or 20% CP administration reduced the triglyceride and cholesterol concentrations, while enhanced high-density lipoprotein cholesterol (HDL-C) concentration in serum. Western blot analysis showed that piglets in the 20% CP group had higher protein abundance of hormone-sensitive triglyceride lipase (HSL) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), as compared with other groups. Moreover, the mRNA expression of sterol regulatory element binding transcription factor 1 (SREBPF1), fatty acid synthase (FASN), and stearoyl-CoA desaturase (SCD) were lower in the 17% or 20% CP group, compared with those of the piglets administered with 14% CP. Of note, the mRNA level of acetyl-CoA carboxylase alpha (ACACα) was lower in the 17% CP group, compared with other groups. Additionally, the mRNA level of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor alpha α (PPARα), glucose-6-phosphatase catalytic subunit (G6PC), and phosphoenolpyruvate carboxykinase 1 (PKC1) in the liver of piglets in the 20% CP group were higher than those of the 14% CP group. Collectively, our results demonstrated that dietary CP could regulate hepatic lipid metabolism through altering hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis.

Improvement effect and mechanism of ethanol extract from Citri Reticulatae Pericarpium on triglyceride in hyperlipidemia model rat

The aim of this paper was to study the improvement effect of ethanol extract from Citri Reticulatae Pericarpium(CRP) on triglyceride of hyperlipidemia model rats, and to explore the possible mechanism. SD rats were randomly divided into normal group, model group, positive control group, and high, medium and low-dose CRP ethanol extract groups, with 10 rats in each group. During the experiment, except for the normal group that was fed with distilled water and ordinary feed, rats in the other groups were given different concentrations of alcohol and fed with high-sugar and fat diets. All rats were given free diets. While being modeled, each group was administered with 0.01 mL·g~(-1) by gavage once a day for six weeks. Blood samples were collected after two weeks, four weeks and six weeks of drug treatment. After the completion of the experiment, blood, liver and adipose tissue were collected. Triglyceride(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum, TG in liver tissue and TG in fecal were detected. Free fatty acid(FFA) and triglyceride-related hydrolase, such as adipose tiglyceride lipase(ATGL), lipoprotein lipase(LPL), hepatic lipase(HL), hormone-sensitive triglyceride lipase(HSL) were detected by ELISA. The mRNA expressions of peroxisome proliferators-activated receptors(PPARγ), sterol regulatory element binding protein 1 c(SREBP-1 c) and farnesoid X receptor(FXR) were determined by RT-PCR. Compared with the model group, each administration group could reduce TG levels in serum and liver to varying degrees, reduce serum ALT, AST, ALP activities, significantly reduce free fatty acid content in serum, significantly increase triglyceride metabolism-related enzymes, including fat ATGL, LPL and liver HL content, and significantly reduced the content of fat HSL. According to the study of transcriptional regulation genes relating to triglyceride metabolism, extract from CRP could significantly increase the mRNA expressions of PPARγ and FXR. In conclusion, ethanol extract from CRP could ob-viously reduce the TG level of hyperlipidemia model rats, and might reduce plasma TG content by increasing PPARγ-LPL/ATGL and FXR-HL triglyceride hydrolysis pathways.

Inhibition of fatty acid oxidation induced by up-regulation of miR-124 and miR-205 during exposure of largemouth bass (Micropterus salmoides) to acute hypoxia

With increased breeding density, the possibility of hypoxia increases. This study simulated the hypoxic environment (1.2 ± 0.2 mg / L) that may occur within 24 h of aquaculture to stress largemouth bass (Micropterus salmoides). The effects of this environment on related enzymes and genes were examined to explore the effects of hypoxia on lipid metabolism in the liver. Hypoxic stress increased liver triglyceride and non-esterified fatty acid content, and increased lipase (LPS) and lipoprotein lipase (LPL) activities related to fat mobilization. Hypoxia stress also significantly increased the expression levels of genes involved in fatty acid activation and fatty acid transport, including hormone-sensitive triglyceride lipase (HSL), solute carrier family member 27 member 6 (SLC27A6), peroxisomal proliferation activated receptor alpha (PPARA,) and acyl-CoA synthase long-chain family 4 (ACSL4). However, hypoxia stress significantly reduced the expression level of the carnitine palmitoyltransferase 1 (CPT-1) gene, with a downward trend of enzyme activity. The decreased level of CPT-1 was explained by negative regulation by miR-124 and miR-205, as measured by quantitative polymerase chain reaction and dual-luciferase reporter assays. Overall, acute hypoxic stress enhanced lipid mobilization, fatty acid activation, and fatty acid transport, but inhibited fatty acid oxidation by miR-124 and miR-205 down-regulation of CPT-1 expression. These findings provide new insights into the regulation of lipid metabolism in fish under hypoxic stress.

The effect of oxidized fish oil on lipid metabolism in Rhynchocypris lagowski Dybowski

Fish oil can not only provide energy for the growth and development of fish, but also constitute a variety of tissue and cellular structural components of fish. However, fish oil is easily oxidized in the process of feed processing, treatment and storage, which reduces the feed quality and threatens the health of fish. Therefore, the purpose of this study was to investigate the effects of different degrees of oxidation of fish oil in feed on fatty acid composition and lipid metabolism in hepatopancreas of Rhynchocypris lagowski Dybowski. Five diets containing five oxidation levels (0, 100, 200, 300 and 400 meq/kg) of fish oil were formulated and fed to 525 healthy R. lagowski (4.48 ± 0.14 g) that were randomly divided into 15 glass aquariums. After 8 weeks, hepatopancreas samples were taken for fatty acid composition, and biochemical analysis. The results showed that the content of Polyunsaturated fatty acid (PUFA) in muscle of R. lagowski increased significantly with the increase of oxidation degree of fish oil (P < 0.05), but there were no changes in Saturated fatty acid (SFA), Monounsaturated fatty acid (MUFA), EPA (C20:5n3), and ∑n-6 (P>0.05). Compared with the control group, the contents of SFA, MUFA and EPA in hepatopancreas were significantly increased (P < 0.05), while DHA (C22:6n3), ∑n-3, ∑n-6, and PUFA were decreased (P < 0.05). Feeding with OFO increased hepatopancreas total cholesterol (TC), triacylglycerol (TG), HDL/LDL ratio, FAS, and ACCα that involved in lipid synthesis enzymes (P < 0.05), while reduced liver esterase (HL), fatty acyl-CoA synthetase (ACS), carnitine palmitoyltransferase (CPT-1) and hormone-sensitive triglyceride lipase α (HSLα) enzyme activity and gene expression that associated with lipid decomposition (P < 0.05). It is suggested that the adverse effects of dietary oxidized oil may be achieved by promoting fatty acid synthesis, inhibiting fatty acid oxidation, increasing fatty acid uptake by hepatopancreas and reducing the ability of TG to transport from hepatopancreas to extrahepatic tissues, thus inducing fat accumulation in hepatopancreatic cells and further affecting lipid metabolism in hepatopancreas.

Jiang Gui Fang activated interscapular brown adipose tissue and induced epididymal white adipose tissue browning through the PPARγ/SIRT1-PGC1α pathway.

Gui Zhi Tang, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, has been widely used to treat exogenous cold for thousands of years. Recent studies have shown that Gui Zhi Tang has the effect of regulating the body temperature. Because of its effect on heat production, protecting vital organs of the body and avoiding damage from the cold environment, Jiang Gui Fang (JG) was obtained from the Department of Traditional Chinese Medicine at the General Hospital of Northern Theatre Command where it has been used clinically for many years and has exhibited favourable efficacy. Based on research on Gui Zhi Tang, the principles of traditional Chinese medicine and survey of a large number of studies, this empirical formula was developed. The composition of JG included Dried ginger, Cassia twig, and Liquorice in Gui Zhi Tang, which play a major role in the treatment of exogenous cold, and combined these components with other Chinese medicines, such as Pueraria, Spatholobus, Acanthopanacis cortex, Evodiae fructus, and Codonopsis pilosula. To promote the core body temperature and prevent invasion of the major organs from the cold environment, we studied the effect of JG on the core body temperature of mice and then explored its regulation of interscapular brown adipose tissue (iBAT) and epididymal white adipose tissue (eWAT) and the possible mechanism. Finally, we determined the phytochemical composition of JG that plays a role in heat production. In vivo study, we performed a 4-week treatment of JG in acute cold environment at -20 °C and chronic cold exposure at 4 °C. The core temperature, adipose tissue weight, serum parameters, and morphological observation of adipocytes, liver and kidney were measured. Then we investigated the expression levels of adipogenic factors, thermogenic factors and lipoprotein. In vitro, we determined the lipid droplet content, ATP content, and the maximum oxygen consumption of mitochondria. JG treatment promoted core temperature, inhibited eWAT weight, protected liver, and reduced glucose and lipids in Kunming (KM) mice. JG also increased the expression of BAT-associated thermogenic factors, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α). The levels of the lipogenic factor peroxisome proliferate-activator receptor gamma (PPARγ) and the lipolytic protein hormone-sensitive triglyceride lipase (HSL) in eWAT were elevated. The results of H&E and immunohistochemistry showed that JG significantly reduced the size of iBAT and eWAT and increased the content of UCP1. In vitro, JG reduced the content of lipid droplets and ATP in brown fat cells. The maximum oxygen consumption capacity of mitochondria and the expression levels of UCP1, PGC1α and silent mating type information regulation 2 homologue 1 (SIRT1) were enhanced after JG treatment. In vivo and in vitro studies, the results demonstrated that JG obviously increased the core temperature of mice by activating iBAT and inducing eWAT browning, which proved the mechanism is closely related to the PPARγ/SIRT1- PGC1α pathway. In this paper, we will provide a reference for further study of iBAT activation and eWAT browning.

Growth, biochemical, fatty acid composition, and mRNA levels of hepatic enzymes in genetically improved farmed tilapia (GIFT,Oreochromis niloticus) (Linnaeus, 1758) at different stocking densities

Investigated were the effects of stocking density on juvenile growth performance, serum biochemistry, fatty acid composition, and mRNA levels of enzymes involved in lipid metabolism in genetically improved farmed tilapia (GIFT), Oreochromis niloticus. Juvenile fish (n = 900) were distributed into 15 tanks at five initial stocking densities (75, 150, 225, 300, and 375 g/m3 per 800-L tank, represented as D1–D5, respectively). Temperature was maintained at 28 ± 0.3°C, and water flow rate into the tanks was about 8 L/min. The fish accepted floating pelleted feed (crude protein 28%, crude lipid 6%, and gross energy 149.2 KJ/g diet). The feed amount offered was 4%–8% of body weight. At the end of the 60-day experiment, the final stocking densities were 1,454.18, 2,010.60, 2,913.13, 3,819.73, and 4,380.80 g/m3, respectively. Growth and body mass coefficient of variation were significantly affected (p < .05). No differences in feed conversion rate or survival were found (p > .05). Muscle lipid contents decreased with stocking density from D1 to D5. Serum total protein and cholesterol levels were not affected by the stocking density but the D5 group produced the highest serum cortisol and lactate levels and the lowest glucose levels compared to those of the other groups. Lower muscle saturated fatty acid and n−3 polyunsaturated fatty acid contents were observed in the D4 group than in the other groups, whereas the reverse was found in the n−6 polyunsaturated fatty acid content. Hepatic glucose 6-phosphate dehydrogenase, fatty acid synthetase, hormone-sensitive triglyceride lipase, and lipoprotein lipase mRNA levels were significantly upregulated in response to a high density. These data suggest that the GIFT adapted to high-density conditions by altering the composition of muscle fatty acid and stimulating lipid metabolic enzymes. These mechanisms may help fish respond to high stocking density stress in intensive aquaculture systems.

Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed with a high-fat/cholesterol diet

BackgroundLeucine supplementation has been reported to improve lipid metabolism. However, lipid metabolism in adipose tissues and liver has not been extensively studied for leucine supplementation in mice fed with a high-fat/cholesterol diet (HFCD).DesignC57BL/6J mice were fed a chow diet, HFCD, HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group) or 3% leucine (HFCD+3% Leu group) for 24 weeks. The body weight, peritoneal adipose weight, total cholesterol (TC), triglyceride in serum and liver, and serum adipokines were analyzed. In addition, expression levels of proteins associated with hepatic lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT) browning were determined.ResultsMice in the HFCD group developed obesity and deteriorated lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain and TC levels in circulation and the liver without changing energy intake. The decrease in body fat was supported by histological examination in the WAT and liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin, IL-6, and tumor necrosis factor-alpha, were significantly decreased by supplemented leucine. At the protein level, leucine potently decreased the hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase) and corresponding upstream proteins. In epididymal WAT, the reduced expression levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive lipase and adipose triglyceride lipase, were reversed when leucine was supplemented. Uncoupling protein 1, β3 adrenergic receptors, peroxisome proliferator-activated receptor g coactivator-1α, and fibroblast growth factor 21 were involved in the thermogenic program and WAT browning. Leucine additionally upregulated their protein expression in both WAT and interscapular brown adipose tissue.ConclusionThis study demonstrated that chronic leucine supplementation reduced the body weight and improved the lipid profile of mice fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis, adipocyte lipolysis, and WAT browning.

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

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