Expression Of Lipolytic Genes Research Articles

Taurine Activates SIRT1/AMPK/FOXO1 Signaling Pathways to Favorably Regulate Lipid Metabolism in C57BL6 Obese Mice.

The identification of novel therapeutic agents capable of modulating lipid metabolism holds a promising potential in combating obesity and its associated complications. This study is conducted to evaluate the lipid lowering effect of dietary taurine administration on high-fat fed C57BL6 mice and to study the mechanism by which taurine impacts lipid metabolism. C57BL6 mice are grouped into four (n = 6): i) normal diet (ND), ii) a high-fat diet (HFD), iii) HFD+orlistat (STD), iv) HFD + taurine (TAU) group for 12 weeks. The results show that taurine administration for 12 weeks reduces high fat-induced weight gain, and liver weight when compared with HFD fed mice. It also improves serum biochemical parameters like total cholesterol and triglycerides. Sirtuin 1 (SIRT1) activity, Nicotinamide adenine dinucleotide (NAD+) levels, SIRT1 mRNA, and protein expression are increased in HFD+TAU diet group as compared to HFD group. Taurine treatment suppresses the expression of lipogenic genes (sterol regulatory element binding protein 1c [SREBP1c], fatty acid synthase [FAS], Peroxisome proliferator-activated receptor gamma [PPARγ]) and increases the expression of β-oxidation (peroxisome proliferator-activated receptor alpha [PPARα], liver x receptor beta [LXRβ], peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1α], AMP-activated protein kinase [AMPK]) and lipolytic (forkhead box protein O1 [FOXO1]) genes. Further, taurine mitigates hepatic inflammation by suppressing nuclear factor kappa B (NF-κB) gene expression and pro-inflammatory cytokine markers (IL-6, IL-1β, and TNFα). Taurine exerts lipid lowering effects through activating SIRT1/AMPK/FOXO1 signaling pathways and regulating their downstream targets.

Effects of different sodium acetate levels on growth, antioxidant capacity, and fat deposition in juvenile Onychostoma macrolepis fed a high fat diet

Effects of different sodium acetate levels on growth, antioxidant capacity, and fat deposition in juvenile <i>Onychostoma macrolepis</i> fed a high fat diet

Effects of dietary glutathione on growth performance, muscle quality and lipid metabolism of hybrid crucian carp (Carassius auratus cuvieri ♀ × Carassius auratus red var. ♂) fed a high-fat diet

A 60-day feeding trial was conducted to investigate the influence of glutathione (GSH) on growth performance, lipid metabolism and muscle quality of hybrid crucian carp (initial body weight: 15.03 ± 0.11 g) fed a high-fat diet (HFD). Five experimental diets were prepared in this study: the control diet (6.17% fat), HFD (12.37% fat), and HFD with 200 mg/kg, 400 mg/kg and 600 mg/kg GSH supplementation, respectively. The results indicated that feeding HFD to hybrid crucian carp remarkably reduced weight gain rate (WGR), specific growth rate (SGR), total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activities of serum and liver, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities of liver, but significantly increased malondialdehyde (MDA) content of liver compared to the control group. After adding 200–600 mg/kg GSH to HFD, the WGR, SGR, as well as serum and liver T-AOC activity of hybrid crucian carp increased significantly. Moreover, the supplementation of 400 mg/kg GSH significantly increased the activities of T-SOD, catalase (CAT) of serum and liver, as well as the GSH-Px, glutathione-S-transferase (GST) and GR of liver, but decreased MDA content of serum and liver compared to the HFD. The HFD significantly increased muscle crude lipid, polyunsaturated fatty acids (PUFA) contents and fiber diameter, but decreased chewiness, gumminess, hardness and fiber density compared to the control group. The addition of 400–600 mg/kg GSH significantly increased muscle chewiness, gumminess, hardness, and decreased muscle fiber diameter of HFD-fed hybrid crucian carp. Meanwhile, the addition of 200–600 mg/kg GSH significantly reduced the mono-unsaturated fatty acids (MUFA) content and increased the PUFA content of muscle compared to the HFD. The HFD significantly up-regulated the expression of lipid synthesis genes (dgat2 and srebp1) and down-regulated the expression of lipolysis genes (lpl, hsl and acox1) of liver compared to the control group. The addition of 400–600 mg/kg GSH significantly decreased the expression of lipid synthesis genes (dgat2 and srebp1) and increased the expression of lipolysis genes (hsl, lpl, acox1 and pparα) of HFD-fed hybrid crucian carp. This study demonstrated that GSH effectively ameliorated the decline of growth performance and muscle quality of hybrid crucian carp caused by HFD, and reduced the risk of liver lipid deposition of hybrid crucian carp by regulating the expression of genes related to liver lipid metabolism.

Photoperiod-Dependent Effects of Grape-Seed Proanthocyanidins on Adipose Tissue Metabolic Markers in Healthy Rats.

Variations in photoperiod patterns drive metabolic adaptations in mammals, involving important changes in body weight and adiposity. Moreover, (poly)phenols can help heterotrophs adopt metabolic adaptations to face the upcoming environmental conditions. Particularly, proanthocyanidins from grape-seeds show photoperiod-dependent effects on different metabolic parameters. The present study aims to explore whether grape-seed proanthocyanidin extract (GSPE) consumption differently affects the expression of metabolic markers in WAT (subcutaneous and visceral depots) and BAT in a photoperiod-dependent manner. GSPE (25mgkg-1 day-1 ) is orally administrated for 4 weeks to healthy rats exposed to three photoperiods (L6, L12, and L18). In WAT, GSPE consumption significantly upregulates the expression of lipolytic genes in all photoperiods, being accompanied by increased serum concentrations of glycerol and corticosterone only under the L6 photoperiod. Moreover, adiponectin mRNA levels are significantly upregulated in response to GSPE regardless of the photoperiod, whereas Tnfα and Il6 expression are only downregulated in L6 and L18 photoperiods but not in L12. In BAT, GSPE upregulates Pgc1α expression in all groups, whereas the expression of Pparα is only increased in L18. The results indicate that GSPE modulates the expression of important metabolic markers of WAT and BAT in a photoperiod-dependent manner.

1650-P: Characterizing the Mechanism of Action of the Lipokine 12,13-diHOME

Lipids play an essential role in physiology. In addition to serving as an energy source, bioactive lipids, also known as lipokines, function as signaling molecules regulating metabolism and inflammation. A major source of lipokines, brown adipose tissue (BAT) has been shown to have beneficial effects on cardiometabolic health by increasing energy expenditure and improving glucose tolerance, thus providing a potential target for therapeutic interventions. Recent studies have identified 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME, produced by cytochrome P450-epoxide hydrolase metabolism of linoleic acid (C18:2n-6), as a lipokine produced by BAT that modulates fatty acid uptake (FAU) into brown adipocytes and skeletal muscle cells in response to cold stimulation or exercising, respectively. Here, we characterized the molecular mechanism and structure-activity relationship (SAR) of 12,13-diHOME in BAT fatty acid uptake. Conversion of the terminal carboxylic acid of 12,13-diHOME to ethyl acetate and changes in saturation results in decreased stimulated FAU indicating 12,13-diHOME's activity is structurally dependent. In addition, we provide insight into a novel protein target responsible for enhancing FAU in BAT, in part, by enhancing intracellular calcium mobilization and influencing the expression of lipolytic genes. Furthermore, we have determined that the 12,13-diHOME-stimulated FAU is, in part, dependent on Gq-mediated calcium mobilization as determined by the utilization of Gq inhibitor YM-254890. Thus, the receptor of 12,13-diHOME could represent a target to augment BAT activity by modulating fatty acid metabolism, which could contribute to increased energy expenditure and, consequently, to the prevention of cardiometabolic diseases. Disclosure J.I.Senfeld: None. M.Lynes: None. S.Kodani: None. K.Lee: None. Y.Tseng: Consultant; Cellarity, LyGenesis.

An Artemisia scoparia extract attenuates glucocorticoid-induced lipolysis in adipocytes.

Prescription glucocorticoid (GC) use is widespread across developed countries for the treatment of several inflammatory conditions. Elevated GCs are known to promote lipolysis and metabolic disorders. An extract of Artemisia scoparia (SCO) has been shown to reduce lipolysis and promote metabolic health but has not been investigated in the context of excess GCs. Our aim was to examine the effects of SCO on GC-induced lipolysis. Mature adipocytes were pretreated with vehicle or SCO, then exposed to either the synthetic GC dexamethasone (DEX) or tumor necrosis factor alpha (TNFα). Medium was collected and assayed for glycerol and fatty acids as measures of lipolysis. The expression of several lipolytic genes and proteins was assessed, and the involvement of glucocorticoid receptor (GR) in SCO's effects was also interrogated. SCO significantly attenuated DEX-induced lipolysis but did not interfere with DEX-mediated changes in inflammatory gene profiles in adipocytes. SCO treatment resulted in significant reductions in monomeric phosphodiesterase (PDE) protein levels while elevating PDE multimeric complex formation, but other canonical lipolytic mediators were unaltered. SCO attenuated lipolysis even when GR expression was significantly knocked down. Finally, it was demonstrated that SCO was distinct from rosiglitazone in its antilipolytic effects. SCO attenuates GC-induced lipolysis independently of GR activity. Future studies are needed to elucidate underlying mechanisms.

Concomitant western diet and chronic-binge alcohol dysregulate hepatic metabolism.

There is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) with regards to risk factors and disease progression. However, the mechanism by which fatty liver disease arises from concomitant obesity and overconsumption of alcohol (syndrome of metabolic and alcohol-associated fatty liver disease; SMAFLD), is not fully understood. Male C57BL6/J mice were fed chow diet (Chow) or high-fructose, high-fat, high-cholesterol diet (FFC) for 4 weeks, then administered either saline or ethanol (EtOH, 5% in drinking water) for another 12 weeks. The EtOH treatment also consisted of a weekly 2.5 g EtOH/kg body weight gavage. Markers for lipid regulation, oxidative stress, inflammation, and fibrosis were measured by RT-qPCR, RNA-seq, Western blot, and metabolomics. Combined FFC-EtOH induced more body weight gain, glucose intolerance, steatosis, and hepatomegaly compared to Chow, EtOH, or FFC. Glucose intolerance by FFC-EtOH was associated with decreased hepatic protein kinase B (AKT) protein expression and increased gluconeogenic gene expression. FFC-EtOH increased hepatic triglyceride and ceramide levels, plasma leptin levels, hepatic Perilipin 2 protein expression, and decreased lipolytic gene expression. FFC and FFC-EtOH also increased AMP-activated protein kinase (AMPK) activation. Finally, FFC-EtOH enriched the hepatic transcriptome for genes involved in immune response and lipid metabolism. In our model of early SMAFLD, we observed that the combination of an obesogenic diet and alcohol caused more weight gain, promoted glucose intolerance, and contributed to steatosis by dysregulating leptin/AMPK signaling. Our model demonstrates that the combination of an obesogenic diet with a chronic-binge pattern alcohol intake is worse than either insult alone.

Abstract 148: Lipoprotein Lipase Deficiency Reprograms Bone Marrow Cellular Metabolic Activity And Inflammatory Responses

Objectives: Activated bone marrow (BM) hematopoiesis is associated with systemic inflammation that increases risk for atherosclerosis. We had reported that lipoprotein lipase (LpL), in addition to being a lipolytic enzyme, regulated peripheral and tissue leukocyte levels and affected BM monocyte progenitor differentiation. LpL is mainly expressed in the specialized BM niches. We now questioned the role of LpL in influencing BM microenvironment that affects the homing and differentiation of hematopoietic stem/progenitor cells toward distinct lineages. Methods and Results: We characterized the metabolic and transcriptional phenotypes of BM cells utilizing immunofluorescence, flow cytometry, quantitative RT-PCR, and Seahorse Bioenergetics analysis in transgenic LpL knockout (KO) mice rescued by muscle-specific LpL expression. Differential gene expression (DEG) of BM cells were examined by bulk RNA sequencing (RNAseq). Our data indicate that LpL deficiency reduced expression of key BM vascular niche markers by 2-3-fold (p&lt;0.05), including CD31, Tie-2, endomucin, CXCL12, and CXCR4, as well their associated growth factors - HIF-1α and VEGF. BM vascular endothelial cadherin-labeled cells were decreased by &gt;50% (p&lt;0.05) in LpL KO when compared to that in WT. Cellular uptake of chylomicron-size lipid particles was reduced in LpL KO BM, which may link to metabolic adaptation from mitochondrial oxidative phosphorylation towards glycolysis observed in LpL KO BM (p&lt;0.05). Although the leptin-receptor positive perivascular cells were remained intact, expression of key lipolytic genes, such as ATGL, MGL, and LAL, were markedly reduced by &gt;50% in LpL KO (p &lt; 0.05). KEGG enrichment analysis of DEG shows that LpL KO BM cells had altered hematopoietic lineage signaling pathway. NFκB-directed signaling cascade was also downregulated in LpL KO BM cells, resulting in the reduced expression of pro-inflammatory TNF-α, IL-1β and IL-6. Conclusions: Our results indicate that LpL regulates metabolic activity and inflammatory responses of BM cells. A further understanding of these mechanisms will open the possibilities to target reprogram of both hematopoietic and BM niche cells as a therapeutic strategy to improve atherosclerosis-associated inflammation.

Ameliorating effect of probiotic on nonalcoholic fatty liver disease and lipolytic gene expression in rabbits

Nonalcoholic fatty liver disease (NAFLD) is a condition that affects about 24% of people worldwide. Increased liver fat, inflammation, and, in the most severe cases, cell death are all characteristics of NAFLD. However, NAFLD pathogenesis and therapy are still not clear enough. Thus, this study aimed to determine the effect of a high-cholesterol diet (HCD) inducing NAFLD on lipolytic gene expression, liver function, lipid profile, and antioxidant enzymes in rabbits and the modulatory effects of probiotic Lactobacillus acidophilus (L. acidophilus) on it. A total of 45 male New Zealand white rabbits, eight weeks old, were randomly divided into three groups of three replicates (5 rabbits/replicate). Rabbits in group I were given a basal diet; rabbits in group II were given a high-cholesterol diet that caused NAFLD; and rabbits in group III were given a high-cholesterol diet as well as probiotics in water for 8 weeks. The results showed that a high-cholesterol diet caused hepatic vacuolation and upregulated the genes for lipoprotein lipase (LPL), hepatic lipase (HL), and cholesteryl ester transfer protein (CETP). Downregulated low-density lipoprotein receptor (LDLr) gene, increased liver enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)], cholesterol, triglycerides (TG), low-density lipoprotein (LDL), glucose, and total bilirubin. On the other hand, it decreased high-density lipoprotein (HDL), total protein, albumin, and liver antioxidants [glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)]. Supplementing with probiotics helped to return all parameters to normal levels. In conclusion, probiotic supplementation, especially L. acidophilus, protected against NAFLD, and restored lipolytic gene expression, liver functions, and antioxidants to normal levels.

Effects of dietary adenosine and adenosine 5′-monophosphate supplementation on carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs

This study investigated the effects of adenosine (ADO) and adenosine 5′-monophosphate (AMP) supplementation on the growth performance, carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs. The pigs were allocated to three treatment groups: the control diet, 0.2%ADO diet, or 0.2%AMP diet. Compared with CON group (CON), both ADO and AMP groups increased in carcass straight length (P < 0.05) and decreased in drip loss (P < 0.05), while AMP group tended to increase in redness value (P = 0.05) and decreased in free amino acid content in longissimus thoracis (LT) muscle (P < 0.05). Additionally, ADO or AMP supplementation increased the ADO or AMP content in serum, adipose tissue, and LT muscle (P < 0.05), as well as the protein level of adenosine 2A receptor (A2a) in adipose tissue (P < 0.05). Moreover, both ADO and AMP groups showed an increase in the expression of lipolysis genes (ATGL and HSL) in adipose tissue (P < 0.05). Overall, AMP supplementation could improve meat quality, and ADO and AMP supplementation regulate the lipid metabolism of finishing pigs.

Screening of lncRNA profiles during intramuscular adipogenic differentiation in longissimus dorsi and semitendinosus muscles in pigs

Intramuscular fat content is an important factor that determines meat quality in pigs. In recent years, epigenetic regulation has increasingly studied the physiological model of intramuscular fat. Although long noncoding RNAs (lncRNAs) play essential roles in various biological processes, their role in intramuscular fat deposition in pigs remains largely unknown. In this study, intramuscular preadipocytes in the longissimus dorsi and semitendinosus of Large White pigs were isolated and induced into adipogenic differentiation in vitro. High-throughput RNA-seq was carried out to estimate the expression of lncRNAs at 0, 2 and 8 days post-differentiation. At this stage, 2135 lncRNAs were identified. KEGG analysis showed that the differentially expressed lncRNAs were common in pathways involved with adipogenesis and lipid metabolism. lnc_000368 was found to gradually increase during the adipogenic process. Reverse-transcription quantitative polymerase chain reaction and a western blot revealed that the knockdown of lnc_000368 significantly repressed the expression of adipogenic genes and lipolytic genes. As a result, lipid accumulation in porcine intramuscular adipocytes was impaired by the silencing of lnc_000368. Overall, our study identified a genome-wide lncRNA profile related to porcine intramuscular fat deposition, and the results suggest that lnc_000368 is a potential target gene that might be targeted in pig breeding in the future.

Immuno-metabolic effect of pancreastatin inhibitor PSTi8 in diet induced obese mice: In vitro and in vivo findings

AimsPancreastatin (PST), an anti-insulin peptide derived from chromogranin A. Its levels increase in cases of obesity, which contributes to adipose tissue inflammation and insulin resistance. This study aims to investigate the immunometabolic effect of PST inhibitor (PSTi8) against PST by using in vitro and in vivo finding. Main methods3T3-L1 cells were differentiated with or without PSTi8, and Oil Red O staining was performed. J774A.1 cells were used for macrophage polarization study. The diet-induced obesity and T2DM model was developed in C57BL/6 mice through high-fat diet for 8 weeks. Alzet osmotic pumps were filled with PSTi8 (release rate: 2 mg/kg/day) and implanted in mice for eight weeks. Further, insulin and glucose tolerance tests were performed. Liver and eWAT sections were stained with hematoxylin and eosin. FACS was used to measure mitochondrial ROS and membrane potential, while Oroboros O2k was used to measure oxygen consumption rate. Immunocytochemistry and qRT-PCR were done for protein and gene expression, respectively. Key findingsPSTi8 inhibited the expression of lipolytic genes and proteins in 3T3-L1 adipocytes. PSTi8 improved the inulin sensitivity, lipid profile, MMP, and OCR levels in the 3T3-L1 adipocyte and eWAT. It also increased the M1 to M2 macrophage polarization in J77A.1 cells and eWAT. Further, PSTi8 attenuated inflammatory CD4+ T, CD8+ T cells and increased the anti-inflammatory T-reg and eosinophil populations in the eWAT. It also reduced the expression of pro-inflammatory genes like Mcp1, Tnfα, and Il-6. SignificanceCollectively, PSTi8 exerted its beneficial effect on adipose tissue inflammation and restored energy expenditure against diet-induced obesity.

Chronic Exposure to Low-Molecular-Weight Polycyclic Aromatic Hydrocarbons Promotes Lipid Accumulation and Metabolic Inflammation.

2-naphthol is a low-molecular-weight (LMW) polycyclic aromatic hydrocarbon (PAH) and air pollutant associated with childhood obesity. There has been a recent emergence of studies on the consequences of PAHs on human health. Current epidemiological reports suggest LMW-PAHs may contribute to obesity incidences in children, yet most studies focus on high-molecular-weight PAHs. This study explores 2-naphthol's impact on obesity and obesity-associated metabolic disorders. To investigate 2-naphthol's effect on lipid metabolism and inflammation, we employed 3T3-L1 and BAT1 cell lines to model white and brown adipocytes, respectively, alongside a murine macrophage cell line (RAW264.7). We found that 2-naphthol increased the expression of key adipogenic and lipogenic genes while decreasing lipolytic gene expression in chronically treated 3T3-L1 and BAT1 adipocytes. In addition, chronic 2-naphthol treatment also suppressed adrenergic-stimulated thermogenic gene expression in BAT1 brown adipocytes. In consistence, an increase in lipid accumulation was demonstrated in BODIPY and Oil Red O-stained adipocytes. Additionally, 3T3-L1 adipocytes and RAW264.7 macrophages chronically exposed to 2-naphthol showed upregulated mRNA expression of major inflammatory cytokines (e.g., tumor necrosis factor α (Tnfα), interleukin-1β (Il-1β), and Il-6). In summary, chronic exposure to 2-naphthol stimulates lipid accumulation in adipocytes and inflammation in adipocytes and macrophages. These findings support previous research that demonstrates 2-naphthol has obesogenic potential.

Muscle characteristics comparison and targeted metabolome analysis reveal differences in carcass traits and meat quality of three pig breeds.

This study investigated the molecular basis for differences in meat yield and quality between Duroc, Taoyuan black (TB), and Xiangcun black (XB) pigs. The results show that TB pigs have lower carcass weight, lean percentage, pH decline, and glycolytic potential but have higher fat percentage, water- holding capacity, intramuscular fat content, antioxidant capacity, and percentage of slow-twitch fibers than the Duroc pigs. Moreover, muscles of TB pigs have lower protein synthesis and lipolysis gene expression than the muscles of Duroc pigs. Targeted metabolome analysis indicates that 24 metabolites significantly differ among these three pig breeds. Correlation analysis suggests that L-malic acid and β-alanine contents in muscle are closely related to meat quality. These findings suggest that the excellent meat quality of TB pigs is closely related to muscle metabolism and fiber characteristics, while lower protein synthesis and lipolysis may contribute to less meat yield.

Anti-pancreatic lipase and anti-adipogenic effects of 5,7,3′,4′,5′-pentamethoxy and 6,2′,4′-trimethoxy flavone - An in vitro study

In this study, the anti-obesity effects of 5,7,3′,4′,5′-pentamethoxyflavone (PMF) and 6,2′,4′-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.

Nuclease treatment enhanced the ameliorative effect of yeast culture on epidermal mucus, hepatic lipid metabolism, inflammation response and gut microbiota in high-fat diet-fed zebrafish

As a functional feed additive, yeast cultures are rich in nucleotides, and adding extra nuclease can significantly increase the content of nucleotides in yeast culture. In this experiment, the effects on growth, epidermal mucus, liver and intestinal health of zebrafish were evaluated by supplementing the yeast culture or nuclease-treated yeast culture with a high-fat diet (HFD). One-month-old zebrafish were fed four diets: normal diet (NORM), HFD, yeast culture diet (YC), and nuclease-treated yeast culture diet (YC (N)) for three weeks. Results showed that the complement 4 activity of the epidermal mucus in YC (N) group was significantly higher than those in HFD and YC groups (P < 0.05). The YC and YC (N) significantly reduced the content of hepatic triglyceride caused by HFD (P < 0.05). Moreover, compared with the YC group, the YC (N) significantly increased the expression of lipolysis genes, such as PPARα, PGC1α, ACOX3 (P < 0.05). Compared with the YC group, the YC (N) group significantly increased the expression of liver pro-inflammatory factors TNFα, IL-6, IL-1β and anti-inflammatory factors TGFβ, IL-10 (P < 0.05). The diet YC and YC (N) significantly improved the height of the intestinal villus (P < 0.05). Compared with the HFD group, the YC (N) group significantly increased the expression of intestinal pro-inflammatory factors TNFα, IL-6 and anti-inflammatory factors TGFβ, IL-10 (P < 0.05). The YC (N) group significantly decreased the abundance of intestinal Proteobacteria and Acinetobacter, and increased the abundance of intestinal Actinobacteria, Mycobacterium and Rhodobacter (P < 0.05). In conclusion, compared with the supplement of yeast culture, nuclease treated yeast culture can further alleviate the adverse effects of HFD on liver and intestinal health, and be used as feed additives for the nutritional and immune regulation of fish.

OR23-1 FXR Regulates the Expansion and Metabolic Function of Adipose Tissue upon Caloric Excess

Abstract Obesity is a major risk factor for developing metabolic diseases. Adipose tissue stores excess calories during obesity. Nuclear receptor Farnesoid X receptor (FXR) is expressed in various tissues and transcriptionally regulates lipid and glucose metabolism. However, the role of FXR in regulating adipose expansion is unknown. We showed that Fxr transcript is expressed in mature adipocytes isolated from both white (WAT) and brown (BAT) adipose tissues. In adipocyte-specific Fxr knockout (Ad-FxrKO) mice, we found enlarged adipocytes and decreased expression of lipolytic genes upon 60% high fat diet (HFD) or high fat/high sucrose western diet challenge. Transcriptomic analysis of WAT from Ad-FxrKO and control mice upon chow or HFD revealed that many genes involved in glucose and lipid homeostasis are misregulated in Ad-FxrKO mice with distinct patterns under normal and obese conditions. Since WAT stores fat and BAT generates heat, we examined both these depots in Ad-FxrKO mice and found reductions in the expression of mitochondrial genes and energy expenditure. Intriguingly, we found ectopic fat accumulation in the liver and systemic glucose intolerance in Ad-FxrKO compared to the control mice during obesity. Overall, these findings implicate that FXR may regulate lipid metabolism and mitochondrial functions in the adipose tissue, which consequently impacts whole-body energy homeostasis. Presentation: Monday, June 13, 2022 11:15 a.m. - 11:30 a.m.

Cdo1 promotes PPARγ-mediated adipose tissue lipolysis in male mice.

Cysteine dioxygenase 1 (Cdo1) is a key enzyme in taurine synthesis. Here we show that Cdo1 promotes lipolysis in adipose tissue. Adipose-specific knockout of Cdo1 in mice impairs energy expenditure, cold tolerance and lipolysis, exacerbates diet-induced obesity (DIO) and decreases adipose expression of the key lipolytic genes encoding ATGL and HSL, with little effect on adipose taurine levels. White-adipose-specific overexpression of ATGL and HSL blunts the role of adipose Cdo1 deficiency in promoting DIO. Mechanistically, Cdo1 interacts with PPARγ and facilitates the recruitment of Med24, the core subunit of mediator complex, to ATGL and HSL gene promoters, thereby transactivating their expression. Further, mice with transgenic overexpression of Cdo1 show better cold tolerance, ameliorated DIO and higher lipolysis capacity. Thus, we uncover an unexpected and important role of Cdo1 in regulating adipose lipolysis.

Modulatory Effects of Probiotic Lactobacillus acidophilus On Expression of Lipolytic Genes, Carcass Traits and Growth Performance in New Zealand White Rabbit

Modulatory Effects of Probiotic Lactobacillus acidophilus On Expression of Lipolytic Genes, Carcass Traits and Growth Performance in New Zealand White Rabbit

Expression patterns of AMPK and genes associated with lipid metabolism in newly hatched chicks during the metabolic perturbation of fasting and refeeding

Fasting-refeeding perturbation has been extensively used to reveal specific genes and metabolic pathways that control energy metabolism in chickens. In this study, 200 chickens were randomly assigned to 2 groups after hatching: the control group (C, fed ad libitum) and the fasting-refeeding group (T, water ad libitum). The chicks in Group T were fasted for 72 h, and then fed for another 48 h. Liver, hypothalamus, and adipose samples were collected at 0 (F0), 24 (F24), 48 (F48), and 72 h (F72) after fasting and 4 (FR4), 12 (FR12), 24 (FR24), and 48 h (FR48) after refeeding, respectively. Results showed that Group T had a significantly higher number of liver vacuoles (P < 0.05 or P < 0.01) and a significantly lower gray value of Sudan IIIstained sections (P < 0.05 or P < 0.01) than Group C at F48-FR48. In addition, compared with the Group C, fasting and refeeding reduced the expression of stearoyl CoA desaturase (SCD) mRNA (P < 0.05 or P < 0.01) in the liver and adipose tissues, the expression of glucocorticoid receptor (GR) mRNA (P < 0.05 or P < 0.01) in the liver, adipose, and hypothalamus tissues, and the expression of fatty acid synthase (FAS) mRNA (P < 0.05 or P < 0.01) in the liver at F24-FR24. Moreover, relative to those in Group C, fasting and refeeding increased the mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK) α, AMPKβ, and AMPKγ in the hypothalamus (P < 0.05 or P < 0.01) at F24-FR24. In conclusion, fasting and refeeding increased the fat content of the liver, and the expression of lipolytic genes in the hypothalamus (e.g., AMPKα, AMPKβ, and AMPKγ) but decreased the expression of fat synthesis genes in the liver (e.g., SCD, GR, and FAS), adipose (SCD and GR), and hypothalamus (GR).