Analysis of the population genetic structure using microsatellite markers in goat populations in Taiwan.

Due to the poor growth rate of the Taiwan black (TB) goat in Taiwan, many exotic breeds were brought into breeding schemes to improve TB goat. However, the excessive cross-breeding of alien species with TB goat has decreased its population numbers, genetic variation and biodiversity. Therefore, TB goat population considered an endemic species in Taiwan that needed to be conservation. The objective of the present study was to analyze the genetic structure and TB goat using genetic markers for genetic improvement and to sustain germplasm conservation and utilization. 15 microsatellite markers, divided into three sets, were used to analyze 690 goats sampled from 10 goat populations. The average number of alleles (Na) and effective alleles (Ne) was 11.87 ± 3.93 and 5.093 ± 1.768, respectively. The average expected heterozygosity (HE) and observed heterozygosity (HO) was 0.780 ± 0.084 and 0.602 ± 0.116, respectively. The average polymorphic information content (PIC) was 0.747 ± 0.103; FIS was 0.058 ± 0.075. All 15 microsatellite markers were highly polymorphic. The genetic distances between individuals were estimated to construct a phylogenetic tree. In present study, the 690 goat samples were divided into 8 clusters. The results indicated that these 15 microsatellite markers successfully clustered goat populations in Taiwan and could assist in the preservation of TB goats.

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator's, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1ß secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.

Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice.

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing "healthy obese" by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [18F] fluorodeoxyglucose-PET/CT (18F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.

The impact of DRP1 on myocardial fibrosis in the obese minipig.

BACKGROUND: The heart is a highly oxidative tissue, thus mitochondria play a major role in maintaining optimal cardiac function. Our previous study established a dietary-induced obese minipig with cardiac fibrosis. The aim of this study was to elucidate the role of mitochondrial dynamics in cardiac fibrosis of obese minipigs. DESIGN: Four-month-old Lee-Sung minipigs were randomly divided into two groups: a control group (C) and an obese group (O) by feeding a control diet or a high-fat diet (HFD) for 6 months. Exposure of H9c2 cardiomyoblasts to palmitate was used to explore the effects of high-fat on induction of myocardial injury in vitro. RESULTS: The O pigs displayed greater heart weight and cardiac collagen accumulation. Obese pigs exhibited a lower antioxidant capacity, ATP concentration, and higher oxidative stress in the left ventricle (LV). The HFD caused downregulation in protein expression of PGC-1α and OPA1, and upregulation of DRP1, FIS1, and PINK1 in the LV of O compared to C pigs. Furthermore, palmitate induced apoptosis and decreased ATP content in H9c2 cells. Palmitate elevated the protein expression of DRP1 and PINK1 in these cells. Inhibition of DRP1 protein expression by siDRP1 in H9c2 cells resulted in enhanced ATP and decreased palmitate-induced apoptosis. CONCLUSIONS: These results suggest that mitochondrial dynamics were linked to the progression of obesity-related cardiac injury. Inhibition of DRP1 after palmitate exposure in H9c2 cells resulted in improved ATP level and decreased apoptosis in vitro suggesting that mitochondrial fission serves a key role in progression of obesity-induced cardiac fibrosis.

LRRK2 Regulates CPT1A to Promote ß-Oxidation in HepG2 Cells.

Leucine-rich repeat kinase 2 (LRRK2) is involved in lipid metabolism; however, the role of LRRK2 in lipid metabolism to affect non-alcoholic fatty liver disease (NAFLD) is still unclear. In the mouse model of NAFLD induced by a high-fat diet, we observed that LRRK2 was decreased in livers. In HepG2 cells, exposure to palmitic acid (PA) down-regulated LRRK2. Overexpression and knockdown of LRRK2 in HepG2 cells were performed to further investigate the roles of LRRK2 in lipid metabolism. Our results showed that ß-oxidation in HepG2 cells was promoted by LRRK2 overexpression, whereas LRRK2 knockdown inhibited ß-oxidation. The critical enzyme of ß-oxidation, carnitine palmitoyltransferase 1A (CPT1A), was positively regulated by LRRK2. Our data suggested that the regulation of CPT1A by LRRK2 may be via the activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα). The overexpression of LRRK2 reduced the concentration of a pro-inflammatory cytokine, tumor necrosis factor α (TNFα), induced by PA. The increase in ß-oxidation may promote lipid catabolism to suppress inflammation induced by PA. These results indicated that LRRK2 participated in the regulation of ß-oxidation and suggested that the decreased LRRK2 may promote inflammation by suppressing ß-oxidation in the liver.

Monitoring of genetically close Tsaiya duck populations using novel microsatellite markers with high polymorphism.

OBJECTIVE: A set of microsatellite markers with high polymorphism from Tsaiya duck were used for the genetic monitoring and genetic structure analysis of Brown and White Tsaiya duck populations in Taiwan. METHODS: The synthetic short tandem repeated probes were used to isolate new microsatellite markers from the genomic DNA of Tsaiya ducks. Eight populations, a total of 566 samples, sourced from Ilan Branch, Livestock Research Institute were genotyped through novel and known markers. The population genetic variables were calculated using optional programs in order to describe and monitor the genetic variability and the genetic structures of these Tsaiya duck populations. RESULTS: In total 24 primer pairs, including 17 novel microsatellite loci from this study and seven previously known loci, were constructed for the detection of genetic variations in duck populations. The average values for the allele number, the effective number of alleles, the observed heterozygosity, the expected heterozygosity, and the polymorphism information content were 11.29, 5.370, 0.591, 0.746, and 0.708, respectively. The results of analysis of molecular variance and principal component analysis indicated a contracting Brown Tsaiya duck cluster and a spreading White Tsaiya duck cluster. The Brown Tsaiya ducks and the White Tsaiya ducks with Pekin ducks were just split to six clusters and three clusters when K was set equal to 6 and 3 in the Bayesian cluster analysis. The individual phylogenetic tree revealed eight taxa, and each individual was assigned to its own population. CONCLUSION: According to our study, the 24 novel microsatellite markers exhibited a high capacity to analyze relationships of inter- and intra-population in those populations with a relatively limited degree of genetic diversity. We suggest that duck farms in Taiwan could use the new (novel) microsatellite set to monitor the genetic characteristics and structures of their Tsaiya duck populations at various intervals in order to ensure quality breeding and conservation strategies.

The role of pericardial adipose tissue in the heart of obese minipigs.

BACKGROUND: Pericardial adipose tissue (PAT) volume is highly associated with the presence and severity of cardiometabolic diseases, but the underlying mechanism is unknown. We previously demonstrated that a high-fat diet (HFD) induced metabolic dysregulation, cardiac fibrosis and accumulation of more PAT in minipigs. This study used our obese minipig model to investigate the characteristics of PAT and omental visceral fat (VAT) induced by a HFD, and the potential link between PAT and HFD-related myocardial fibrosis. MATERIALS AND METHODS: Five-month-old Lee-Sung minipigs were made obese by feeding a HFD for 6 months. RESULTS: The HFD induced dyslipidemia, cardiac fibrosis and more fat accumulation in the visceral and pericardial depots. The HFD changes the fatty acid composition in the adipose tissue by decreasing the portion of linoleic acid in the VAT and PAT. No arachidonic acid was detected in the VAT and PAT of control pigs, whereas it existed in the same tissues of obese pigs fed the HFD. Compared with the control pigs, elevated levels of malondialdehyde and TNFα were exhibited in the plasma and PAT of obese pigs. HFD induced greater size of adipocytes in VAT and PAT. Higher levels of GH, leptin, OPG, PDGF, resistin, SAA and TGFß were observed in obese pig PAT compared to VAT. CONCLUSION: This study demonstrated the similarities and dissimilarities between PAT and VAT under HFD stimulus. In addition, this study suggested that alteration in PAT contributed to the myocardial damage.

Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease.

BACKGROUND: Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. METHODS: We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. We also treated a THP-1 macrophage and a HT-29 colon epithelial cell line with ADN recombinant protein to study the effects of ADN on inflammation. RESULTS: After inducing murine colitis, pAdipoR1 mice developed more severe symptoms than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells. Moreover, we also observed that the expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. CONCLUSIONS: Our study showed that ADN-AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and recruited neutrophils into the colonic tissue to increase inflammation.

Expression profile of adiponectin and adiponectin receptors in high-fat diet feeding chickens.

Adiponectin is a circulatory cytokine secreted from adipose tissues and exerts critical metabolic functions in mammals. However, expression profiles of adiponectin and adiponectin receptors in the avian species that may be very different from mammals, especially under affluent nutrition conditions, remain unexplored to examine the effects of adiponectin and adiponectin receptors in chicken adipose tissues under high-fat diet (HFD) feeding. Twenty Taiwan country chickens (L2 bred) of 12 weeks old were challenged with a 10% high-fat diet for 6 weeks. Results showed that body weights and plasma triglycerides, cholesterol and dipeptidyl peptidase-4 (DPP4) were all increased in the HFD treatments. Interestingly, we first demonstrated that chicken circulating macromolecule adiponectin and fat disulphide-bond A oxidoreductase-like protein (DsbA-L), a regulator involved in adiponectin secretion, were elevated upon HFD feeding. Moreover, the mRNA expression of adiponectin and adiponectin receptors as well as additional adipose-related genes such as fatty acid synthase (FAS), adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL), and peroxisome proliferator-activated receptor γ (PPARγ) were also increased in the chicken abdominal fats under HFD conditions. These results suggest that HFD treatment alters adiponectin and metabolic genes in chicken adipose tissues. In conclusion, in the present study, we examine expression profiles of adiponectin, adiponectin receptors, adiponectin secretion regulator DsbA-L, and metabolic genes in chicken fats upon HFD supplementation and provide new insights for how adiponectin entail the pathophysiologically obesogenic conditions in the avian species.

Survey of genetic structure of geese using novel microsatellite markers.

OBJECTIVE: The aim of this study was to create a set of microsatellite markers with high polymorphism for the genetic monitoring and genetic structure analysis of local goose populations. METHODS: Novel microsatellite markers were isolated from the genomic DNA of white Roman geese using short tandem repeated probes. The DNA segments, including short tandem repeats, were tested for their variability among four populations of geese from the Changhua Animal Propagation Station (CAPS). The selected microsatellite markers could then be used to monitor genetic variability and study the genetic structures of geese from local geese farms. RESULTS: 14 novel microsatellite loci were isolated. In addition to seven known loci, two multiplex sets were constructed for the detection of genetic variations in geese populations. The average of allele number, the effective number of alleles, the observed heterozygosity, the expected heterozygosity, and the polymorphism information content were 11.09, 5.145, 0.499, 0.745, and 0.705, respectively. The results of analysis of molecular variance and principal component analysis indicated a contracting white Roman cluster and a spreading Chinese cluster. In white Roman populations, the CAPS populations were depleted to roughly two clusters when K was set equal to 6 in the Bayesian cluster analysis. The founders of private farm populations had a similar genetic structure. Among the Chinese geese populations, the CAPS populations and private populations represented different clads of the phylogenetic tree and individuals from the private populations had uneven genetic characteristics according to various analyses. CONCLUSION: Based on this study's analyses, we suggest that the CAPS should institute a proper breeding strategy for white Roman geese to avoid further clustering. In addition, for preservation and stable quality, the Chinese geese in the CAPS and the aforementioned proper breeding scheme should be introduced to geese breeders.

Cytoophidium assembly reflects upregulation of IMPDH activity.

Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) (both of which have two isoforms) can form fiber-like subcellular structures termed 'cytoophidia' under certain circumstances in mammalian cells. Although it has been shown that filamentation of CTPS downregulates its activity by disturbing conformational changes, the activity of IMPDH within cytoophidia is still unclear. Most previous IMPDH cytoophidium studies were performed under conditions involving inhibitors that impair GTP synthesis. Here, we show that IMPDH forms cytoophidia without inhibition of GTP synthesis. First, we find that an elevated intracellular CTP concentration or treatment with 3'-deazauridine, a CTPS inhibitor, promotes IMPDH cytoophidium formation and increases the intracellular GTP pool size. Moreover, restriction of cell growth triggers the disassembly of IMPDH cytoophidia, implying that their presence is correlated with active cell metabolism. Finally, we show that the presence of IMPDH cytoophidia in mouse pancreatic islet cells might correlate with nutrient uptake in the animal. Collectively, our findings reveal that formation of IMPDH cytoophidia reflects upregulation of purine nucleotide synthesis, suggesting that the IMPDH cytoophidium plays a role distinct from that of the CTPS cytoophidium in controlling intracellular nucleotide homeostasis.

Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens.

Background: Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model.Objective: The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis.Methods: Hy-Line W-36 laying hens were fed standard feed from 25 to 45 wk of age to induce fatty liver. They were killed every 4 wk, and liver and plasma were collected at each time point to assess fatty liver development and for transcriptomic and proteomic analysis. Next, selected biomarkers were confirmed in additional experiments by providing supplements of the hepatoprotective nutrients betaine [300, 600, or 900 parts per million (ppm) in vivo; 2 mM in vitro] or docosahexaenoic acid (DHA; 1% in vivo; 100 µM in vitro) to 30-wk-old Hy-Line W-36 laying hens for 4 mo and to Hy-Line W-36 chicken primary hepatocytes with oleic acid-induced steatosis. Liver or hepatocyte lipid contents and the expression of biomarkers were then examined.Results: Plasma acetoacetyl-CoA synthetase (AACS), dipeptidyl-peptidase 4 (DPP4), glutamine synthetase (GLUL), and glutathione S-transferase (GST) concentrations are well-established biomarkers for NAFLD. Selected biomarkers had significant positive associations with hepatic lipid deposition (P < 0.001). Betaine (900 ppm in vivo; 2 mM in vitro) and DHA (1% in vivo; 100 µM in vitro) supplementation both resulted in lower steatosis accompanied by the reduced expression of selected biomarkers in vivo and in vitro (P < 0.05).Conclusion: This study used adult laying hens to identify biomarkers for NAFLD and indicated that AACS, DPP4, GLUL, and GST could be considered to be potential diagnostic indicators for NAFLD in the future.

Docosahexaenoic acid increases accumulation of adipocyte triacylglycerol through up-regulation of lipogenic gene expression in pigs.

BACKGROUND: Changing dietary fatty acid composition in modern diet influences the prevalence of obesity. Increasing evidences suggest favorable effects of n-3 PUFA for protecting against obesity and the metabolic syndrome. However, the regulation of n-3 PUFA in adipose is still unclear. Thus, this study addressed metabolism of different dietary fats in the adipose tissue of porcine model. METHODS: Eight-week-old cross-bred pigs were randomly assigned to three groups and fed a 2% fat diet for 30 days from either soybean oil (SBO), docosahexaenoic acid (DHA) or beef tallow. An in vitro experiment was conducted in which linoleic acid (LA), DHA or oleic acid (OA) were added to represent the major fatty acid in the SBO-, DHA- or BT- diets, respectively. Adipocytes size and lipid metabolism related genes were analyzed. RESULTS: Plasma triacylglycerol (TAG) was lower in DHA- than in BT-fed pigs, and the product of lipolysis, glycerol was highest in BT-fed pigs. In addition, expression of the lipolytic genes, adipose triglyceride lipase and hormone sensitive lipase was higher in BT-fed pigs and with OA treatment in vitro. DHA promoted protein kinase A activity in pigs without affecting lipolytic genes. Adipocyte cell sizes, TAG content and expression of lipogenic-related genes including, adipose differentiated related protein (ADRP) and diacylglycerol acyltransferase 1 (DGAT1) were elevated by DHA in vivo and in vitro, indicating DHA promoted adipogenesis to trap TAG in adipose tissue. Fatty acid ß-oxidation genes were increased in the DHA-fed pigs. CONCLUSION: This effect was partly explained by the effect of DHA to promote adipogenesis to trap TAG in adipocytes and also increase expression of genes involved in adipocyte fatty acid oxidation. Therefore, our results suggest a direct effect of DHA on adipocyte metabolism, resulting in TAG turnover and fatty acid dissipation to facilitate plasma lipid uptake from the circulation.

Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model.

BACKGROUND: A newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains unsettled. Herein, we reveal the effects of O. formosana in ameliorating hyperglycemia accompanied with depression. METHODS: Diabetes was induced in mice by employing streptozotocin(STZ), a chemical that is toxic to insulin-producing ß cells of the pancreas. These streptozotocin (STZ)-induced diabetic mice showed combined symptoms of hyperglycemia and depressive behaviors. Twenty-four STZ-induced mice were randomly divided into 3 groups subjected to oral gavage with 100 µL solution of either PBS or 25 mg/mL Ophiocordyceps formosana extract (OFE) or 2 mg/mL rosiglitazone (Rosi, positive control group). Treatments were administered once per day for 28 days. An additional 6 mice without STZ induction were treated with PBS to serve as the control group. Insulin sensitivity was measured by a glucose tolerance test and levels of adiponectin in plasma and adipose tissue were also quantified. Behavioral tests were conducted and levels of monoamines in various brain regions relating to depression were evaluated. RESULTS: HPLC analysis uncovered three major constituents, adenosine, D-mannitol and cordycepin, within O. formosana similar to other prestigious medicinal Cordyceps spp.. STZ-induced diabetic mice demonstrated decreased body weight and subcutaneous adipose tissue, while these symptoms were recovered in mice receiving OFE treatment. Moreover, the OFE group displayed improved insulin sensitivity and elevated adiponectin within the plasma and adipose tissue. The anti-depressive effect of OFE was observed in various depression-related behavior tests. Concurrently, neurotransmitters, like 5-HT and dopamine in the frontal cortex, striatum and hippocampus were found to be up-regulated in OFE-treated mice. CONCLUSIONS: Our findings illustrated, for the first time, the medicinal merits of O. formosana on Type I diabetes and hyperglycemia-induced depression. OFE were found to promote the expression of adiponectin, which is an adipokine involved in insulin sensitivity and hold anti-depressive effects. In addition, OFE administration also displayed altered levels of neurotransmitters in certain brain regions that may have contributed to its anti-depressive effect. Collectively, this current study provided insights to the potential therapeutic effects of O. formosana extracts in regards to hyperglycemia and its depressive complications.

Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans.

The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA), DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) exert numerous beneficial effects to maintain physiological homeostasis. In the current review, the physiology of n-3 PUFA effects in the body is delineated from studies conducted in both human and animal experiments. Although mechanistic studies in human are limited, numerous studies conducted in animals and models in vitro provide potential molecular mechanisms of the effects of these fatty acids. Three aspects of n-3 PUFA in adipocyte regulation are discussed: (1) lipid metabolism, including adipocyte differentiation, lipolysis and lipogenesis; (2) energy expenditure, such as mitochondrial and peroxisomal fatty acid ß-oxidation; and (3) inflammation, including adipokines and specialized pro-resolving lipid mediators. Additionally, the mechanisms by which n-3 PUFA regulate gene expression are highlighted. The beneficial effects of n-3 PUFA may help to reduce the incidence of obesity and its comorbidities.

Development of a dietary-induced metabolic syndrome model using miniature pigs involvement of AMPK and SIRT1.

BACKGROUND: During the progression of the metabolic syndrome (MetS), cardiovascular diseases (CVD) appear clinically in many individuals and cause death. As a result, it is essential to set up an optimal animal model to study the mechanism of MetS leading to CVD. SIRT1 and AMPK are the master regulators of lipid and carbohydrate metabolism. The objective of this study was to establish a miniature pig model of Western diet-induced MetS and investigate the role of SIRT1/AMPK during MetS development. MATERIALS AND METHODS: Five-month-old Lee-Sung (LS) and Lanyu (LY) minipigs were each randomly assigned to two groups: control diet (C) and Western diet (W), in a 6-month experimental period. RESULTS: Western diet caused obesity in both minipig models. Compared with the CLS pigs, WLS pigs exhibited hypercholesterolaemia. However, WLY pigs maintained a similar plasma lipid profile to the CLY pigs. Western diet caused a lower antioxidant capacity in the liver of both pig models. WLS pigs had higher triglyceride accumulation in the liver than CLS pigs, whereas WLY and CLY pigs had similar hepatic triglyceride accumulation. Compared with CLS pigs, WLS pigs had a lower hepatic SIRT1 expression, whereas WLY pigs had a higher expression of AMPK, FOXO1 and SIRT1 than CLY pigs. CONCLUSION: Long-term feeding of the Western diet to Lee-Sung miniature pigs not only caused obesity but also induced MetS and fatty liver, whereas Western diet induced obesity in Lanyu pigs without metabolic dysfunctions. SIRT1/AMPK and their downstream pathways might be one of the possible regulators for pathological obesity in Lee-Sung pigs.

Adiponectin receptor 1 enhances fatty acid metabolism and cell survival in palmitate-treated HepG2 cells through the PI3 K/AKT pathway.

PURPOSES: Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the adiponectin receptor 1 (AdipoR1) in HepG2 cells to define the role of adiponectin and its receptor 1 in the development of fatty liver syndrome. METHODS AND RESULTS: Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability. CONCLUSION: AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease.

Adiponectin receptor 1 overexpression reduces lipid accumulation and hypertrophy in the heart of diet-induced obese mice--possible involvement of oxidative stress and autophagy.

BACKGROUND: Studies show that adiponectin and its receptors (AdipoR1 and 2) play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with downregulated adiponectin signaling; however, research has not clarified the functions of AdipoR1 in vivo. METHODS: In this study, mice were induced to overexpress the AdipoR1 transgene so that its functions could be studied in relation to hypertrophic cardiomyopathy. Wild-type and AdipoR1-transgenic male mice were fed ad libitum with a standard chow diet or else a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6-7 weeks of age. RESULTS: After receiving the 24-week HFSD, AdipoR1-transgenic mice did not become obese, nor did they develop heart hypertrophy. The AdipoR1 transgene decreased the elevating cardiac troponin I expression caused by the HFSD. While the HFSD induced mRNA expression of CD36 and CPTI, AdipoR1 reversed it. Suppression of cardiac SOD mRNA expression by the HFSD was improved by the AdipoR1 transgene. The HFSD caused a higher autophagic gene expression of Beclin 1 and Lamp 2 A in the heart, whereas the AdipoR1 transgene ameliorated them. CONCLUSIONS: The AdipoR1 transgene enabled mice to resist diet-induced obesity while decreasing lipid accumulation, oxidative stress and autophagic damage. These effects might contribute to the improvement of heart functions in diet-induced obese mice.

Exploring Bile-Acid Changes and Microflora Profiles in Chicken Fatty Liver Disease Model.

Excessive liver fat causes non-alcoholic fatty liver disease (NAFLD) in laying hens, reducing egg production. Addressing NAFLD via bile-acid metabolism is gaining attention. We induced NAFLD in 7-week-old ISA female chickens with a high-cholesterol, low-choline diet (CLC) for 6 weeks. LC/MS was used to analyze serum and cecal bile acids, while cecal digesta DNA underwent 16S rRNA sequencing. The distribution of bile acid varied in healthy (CON) and CLC-fed chickens. CLC increased secondary bile acids (TLCA, TUDCA, THDCA, TDCA) in serum and primary bile acids (CDCA, TCDCA, isoDCA) in serum, as well as glycochenodeoxycholic acid (GCDCA) in cecal contents. CLC upregulated bile-acid synthesis enzymes (CYP7A1, CYP8B1) in the liver. Bile-acid receptor gene expression (HNF4A, FXR, LXR) was similar between groups. Microbiota abundance was richer in CON (alpha-diversity), with distinct separation (beta-diversity) between CON and CLC. The Firmicutes/Bacteroidetes ratio slightly decreased in CLC. Taxonomic analysis revealed higher Bacteroides, Alistipes, Megamonas in CLC but lower Barnesiella. CLC had more Mucispirillum, Eubacterium_coprostanoligenes_group, Shuttleworthia, and Olsenella, while CON had more Enterococcus, Ruminococcaceae_UCG_014, and Faecalibacterium. This study unveils bile-acid and microflora changes in a chicken NAFLD model, enhancing our understanding of fatty liver disease metabolism and aiding targeted interventions.

Modulation of glucose and lipid metabolism by porcine adiponectin receptor 1-transgenic mesenchymal stromal cells in diet-induced obese mice.

BACKGROUND AIMS: Obesity and its associated diseases demand better therapeutic strategies. Regenerative medicine combined with gene therapy has emerged as a promising approach in various clinical applications. Adiponectin (ApN) and its receptors have been demonstrated to play beneficial roles in modulating glucose and lipid homeostasis. In the current study, we tested such an approach by transplanting mesenchymal stromal cells (MSCs) from porcine ApN receptor (pAdipoR) 1-transgenic mice into high-fat/sucrose diet (HFSD)-fed mice. METHODS: Twenty 6-week-old Friend virus B/NJNarl male mice were randomly assigned into four groups with the control fed a chow diet (chow) and others HFSD for 10 months. The HFSD groups were then intraperitoneally injected once per week for 8 weeks with placebo (200 µL phosphate-buffered saline), wild-type MSC (WT-MSC, 2 × 10(6) cells/200 µL phosphate-buffered saline) or pAdipoR1-transgenic MSC (pR1-tMSC, 2 × 10(6) cells/200 µL phosphate-buffered saline), respectively. Body weights, blood samples, tissue histology, and gene expression and protein levels of metabolism-associated genes were analyzed. RESULTS: Both WT-MSC and pR1-tMSC transplantations restored the messenger RNA expression of AdipoR1, with those of glucose transporter 4 and 5'-adenosine monophosphate-activated protein kinase catalytic subunit α-1 and protein levels of pyruvate kinase induced by pR1-tMSC in the muscles of HFSD-fed mice. In the liver, both WT-MSC and pR1-tMSC ameliorated HFSD-induced hepatosteatosis, with the gene expression of lipoprotein lipase and hormone-sensitive lipase upregulated by the latter. Lastly, pR1-tMSC transplantation reduced fatty acid synthase mRNA levels in the adipose tissues of HFSD-fed mice. CONCLUSIONS: This study demonstrates the modulatory actions of MSC and pR1-tMSC on genes associated with glucose and lipid metabolism and provides insights into its therapeutic application for obesity-associated metabolic complication.