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This study investigated the ameliorative effects of Yinchen lipid-lowering tea (YCLLT) on Non-alcoholic fatty liver disease (NAFLD), the specific mechanism involved was also studied. We modeled hepatocellular steatosis with HepG2 cells and intervened with different concentrations of YCLLT-containing serum. Lipid deposition was assessed by oil red O staining and AdipoR1 expression was analyzed by Western blot. The hepatocyte steatosis model was further treated with YCLLT-containing serum and/or silencing AdipoR1. Lipid deposition was observed by oil red O staining. Flow cytometry was used to detect apoptosis and mitochondrial membrane potential. The levels of TNF-α, IL-6, MDA, 8-OHdG, and ATP were analyzed by ELISA or the corresponding kits. The mitochondrial structure was observed by transmission electron microscopy. The expression of AdipoR1/AMPK/SIRT1 signaling pathway factors was analyzed by Western blot, and co-localization of SIRT1 and immunofluorescence. The results revealed that YCLLT attenuated lipid deposition, inhibited the levels of inflammatory factors TNF-α and IL-6, reduced the levels of MDA and 8-OHdG, up-regulated the ATP content and mitochondrial membrane potential, and promoted the expression of AdipoR1, p-LKB1, p-AMPKα, SIRT1, and PGC-1a in a cellular model of NAFLD. Further, silencing of AdipoR1 inhibited the ameliorative effect of YCLLT in the NAFLD cell model. Altogether, Yinchen lipid-lowering tea attenuates lipid deposition in a fatty liver model by improving mitochondrial function via activating AdipoR1/AMPK/ SIRT1 signaling. [ABSTRACT FROM AUTHOR]

Lipid accumulation and oxidative stress, which could be improved by autophagy, are the "hits" of metabolic-associated fatty liver disease (MAFLD). Ganoderma lucidum spore powder (GLSP) has the effect of improving liver function. However, there are few reports about its effects on and mechanisms impacting MAFLD alleviation. This study investigated the effect of GLSP on hepatic lipid accumulation and oxidative stress and explored the role that autophagy played in this effect. The results showed that GLSP effectively reduced lipid accumulation and activated autophagy in the livers of mice with high-fat-diet-induced disease and palmitic acid-induced hepatocytes. GLSP reduced the lipid accumulation by reducing lipogenesis and promoting lipid oxidation in HepG2 cells. It decreased the production of ROS, increased the activity of SOD and CAT, and improved the mitochondrial membrane potential via the Keap1/Nrf2 pathway. The alleviating effects of GLSP on the lipid accumulation and oxidative stress was reversed by 3-methyladenine (3-MA), an autophagy inhibitor. GLSP activated autophagy via the AMPK pathway in HepG2 cells. In conclusion, GLSP could attenuate MAFLD by the improvement of lipid accumulation and oxidative stress via autophagy. This paper is the first to report the improvement of MAFLD through autophagy promotion. It will shed novel light on the discovery of therapeutic strategies targeting autophagy for MAFLD. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate how dietary arachidonic acid (ARA) level affects growth performance and lipid metabolism in juvenile black seabream (Acanthopagrus schlegelii). A feeding trial was conducted for 8 weeks, during which the fish (0.99 ± 0.10 g) were fed six isonitrogenous and isolipidic diets with varying ARA levels of 0.1%, 0.59%, 1.04%, 1.42%, 1.94%, and 2.42%. Fish fed the diet with 1.42% ARA had significantly higher weight gain (WG) and specific growth rate (SGR) than the other groups (p < 0.05), except for the ARA1.04. As the ARA level increased, the liver and muscle effectively accumulated n−6 polyunsaturated fatty acids (n−6 PUFAs; p < 0.05). However, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n−3 PUFA contents of liver and muscle significantly decreased by increasing dietary ARA level (p < 0.05). Results of liver histology showed dramatically increased vacuolar fat droplets leading to hepatic fat pathological changes in fish fed diets with ARA levels of 1.94% and 2.42% (p < 0.05). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased with increasing dietary ARA level which was accompanied with elevated liver lipid content (p < 0.05). Consistently, triglyceride (TG) and nonesterified fatty acid (NEFA) concentrations of serum and liver, and serum cholesterol (CHO) concentration increased (p < 0.05). As the level of dietary ARA increased, the indicators of lipid metabolism such as sirtuin 1 (sirt1) and peroxisome proliferator‐activated receptor α (pparα) also increased (p < 0.05). However, after reaching their peak in ARA1.04 group, the level of these indicators declined (p < 0.05). The same trend was observed for the expression of genes related to the downstream pathways. While the mRNA levels of sterol regulatory element–binding protein‐1 (srebp-1) and its downstream genes were markedly increased with the increase of dietary ARA level (p < 0.05). In conclusion, these data suggested that the optimum dietary ARA requirement of A. schlegelii is 1.03% of diet based on the WG. The study revealed that a diet containing 1.04% ARA can activate the expression levels of sirt1 and pparα leading to promoted lipolysis. However, dietary ARA levels of ≥1.42% induced lipid accumulation in the liver, as they suppressed the mRNA levels of sirt1 and pparα, while elevating the expression level of genes related to lipogenesis. [ABSTRACT FROM AUTHOR]

Abstract Nano- and microplastics (NMPs) have become a serious global environmental threat that causes damage to mammalian organs. In this work, we investigated the potential molecular mechanism underlying the development of liver fibrosis induced by long-term exposure to three different sized polystyrene (PS)-NMPs (80 nm, 0.5 µm and 5 µm) in mice. Liver fibrosis levels were evaluated in mice after chronic exposure to PS-NMPs. Liver inflammation was mainly increased in chronic exposure to 80 nm and 0.5 µm PS-NMPs. Liver lipid deposition was significantly enhanced after PS-NMPs exposure. However, oxidative stress was not changed under PS-NMPs exposure. GO enrichment and KEGG pathway analyses revealed that the DEGs and shared DEGs were mainly enriched in the metabolism of lipids. The mRNA expression levels of genes related to fatty acid oxidation, synthesis and transport were dramatically induced by PS-NMPs exposure. Four hub genes, Acot3, Abcc3, Nr1i3 and Fmo2, were identified by CytoHubba analysis of shared DEGs. The mRNA expression levels of three hub genes, Acot3, Abcc3 and Nr1i3, were significantly augmented under chronic PS-NMPs exposure. Our results suggest that Acot3, Abcc3 and Nr1i3 are potential molecules involved in the development of liver fibrosis under chronic exposure to PS-NMPs.

Abstract As a member of the p53-binding protein family, apoptosis-stimulating protein p53 2 (ASPP2) is closely related to autophagy and apoptosis. However, the mechanistic role of ASPP2 in the development of metabolic dysfunction-associated steatohepatitis (MASH) remains elusive. Therefore, we investigated the role and underlying mechanisms of ASPP2 in MASH progression in a mouse model of MASH and a cellular model of metabolic dysfunction-associated fatty liver disease. ASPP2 deficiency significantly promoted the inflammatory response, steatosis, and MASH progression in mice. Through transcriptomic analysis, increased ACSL4 expression was identified as a potential key factor. Further elucidation of the underlying mechanisms demonstrated that ASPP2 deficiency increased lipid accumulation and inhibited mitochondrial respiration capacity in HepG2 cells induced by oleic acid. However, silencing of ACSL4 reversed these effects. Thus, our study indicates that ASPP2 is an important regulator of MASH progression through ACSL4 upregulation, highlighting its potential as an alternative approach to MASH treatment.

Transfer RNA-derived small RNAs (tsRNAs) are novel regulatory small non-coding RNAs that have been found to modulate many life activities in recent years. However, the exact functions of tsRNAs in follicle development remain unclear. Follicle development is a remarkably complex process that follows a strict hierarchy and is strongly associated with reproductive performance in ducks. The process of converting small yellow follicles into hierarchal follicles is known as follicle selection, which directly determines the number of mature follicles. We performed small RNA sequencing during follicle selection in ducks and identified tsRNA-00764 as the target of interest based on tsRNA expression profiles in this study. Bioinformatics analyses and luciferase reporter assays further revealed that peroxisome proliferator-activated receptor-γ (PPAR-γ) was the target gene of tsRNA-00764. Moreover, tsRNA-00764 knockdown promoted estrogen and progesterone synthesis and lipid deposition in duck granulosa cells, while a PPAR-γ inhibitor reversed the above phenomenon. Taken together, these results demonstrate that tsRNA-00764, differentially expressed in pre-hierarchal and hierarchy follicles, modulates estrogen and progesterone synthesis and lipid deposition by targeting PPAR-γ in duck granulosa cells, serving as a potential novel mechanism of follicle selection. Overall, our findings provide a theoretical foundation for further exploration of the molecular mechanisms underlying follicle development and production performance in ducks. [ABSTRACT FROM AUTHOR]

Objective: Diabetic nephropathy (DN) is a deleterious microangiopathy of diabetes, constituting a critical determinant of fatality in diabetic patients. This work is purposed to disclose the effects and modulatory mechanism of BTG anti-proliferation factor 2 (BTG2) during the pathological process of DN. Methods: BTG2 expression in kidney tissues of diabetic mice and high glucose (HG)-exposed human proximal tubular cell line HK-2 was assessed with Western blot and RT-qPCR. The diabetic mice model was constructed by streptozotocin injection and confirmed by the blood glucose level beyond 16.7 mmol/L. Hematoxylin and eosin (H&E) staining and measurement of kidney function hallmarks were conducted to assess kidney injury. Cell counting kit (CCK)-8 method and TUNEL assay appraised cell activity and apoptosis. Oil red O staining assayed lipid accumulation. Relevant commercial kits were used to estimate oxidative stress-related factors. Co-immunoprecipitation (Co-IP) assay testified the binding relationship of BTG2 with protein arginine methyltransferase 1 (PRMT1). Results: BTG2 expression was significantly raised in renal tissues of diabetic mice and HK-2 cells exposed to HG. BTG2 deficiency improved viability and extenuated the apoptosis, lipid deposition as well as oxidative stress in HK-2 cells following HG exposure. In addition, PRMT1 was also overexpressed in HK-2 cells exposed to HG. BTG2 interacted with PRMT1 and positively modulated PRMT1 expression. The effects of BTG2 interference on viability, apoptosis, lipid deposition, and oxidative stress in HG-challenged HK-2 cells were partially abrogated by PRMT1 overexpression. Conclusion: Altogether, BTG2 might aggravate HK-2 cell injury in response to HG by binding with PRMT1, providing a novel target for the therapeutic strategy of DN. [ABSTRACT FROM AUTHOR]

Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. Although its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular lipid droplet (LD) content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis lung carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n = 20) were implanted with LLC cells (106) in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red O/lipid staining [tibialis anterior (TA)], and protein (gastrocnemius). LLC mice had a greater number (232%; P = 0.006) and size (130%; P = 0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; P = 0.0109) and "very high" oil-red O positive (178%; P = 0.0002) fibers compared with controls and this was inversely correlated with fiber size (R2 = 0.5294; P < 0.0001). Morphological analyses of LDs show increased elongation and complexity [aspect ratio: intermyofibrillar (IMF) = 9%, P = 0.046) with decreases in circularity [circularity: subsarcolemmal (SS) = 6%, P = 0.042] or roundness (roundness: whole = 10%, P = 0.033; IMF = 8%, P = 0.038) as well as decreased LD-mitochondria touch (−15%; P = 0.006), contact length (−38%; P = 0.036), and relative contact (86%; P = 0.004). Furthermore, dysregulation in lipid metabolism (adiponectin, CPT1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (P < 0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia. NEW & NOTEWORTHY: We sought to advance our understanding of skeletal muscle lipid metabolism and dynamics in cancer cachexia. Cachexia increased the number and size of intramyocellular lipid droplets (LDs). Furthermore, decreases in LD-mitochondrial touch, contact length, and relative contact along with increased LD shape complexity with decreases in circularity and roundness. Dysregulation in lipid metabolism and LD-associated proteins was also documented. Collectively, we show that myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in cancer cachexia. [ABSTRACT FROM AUTHOR]

Glycerol, an abundant by‐product of biodiesel production, has gained attention due to its price and availability for potential commercial applications, and thus utilisation as an animal feed ingredient. This article comprehensively reviews glycerol utilisation in fish and its potential as a dietary ingredient for aquaculture. While dietary inclusion of glycerol may offer cost‐effective energy and metabolic intermediates, studies report inconsistent results regarding its effects on nutrient digestibility, zootechnical performance, and product quality. Recent studies however have demonstrated that dietary glycerol supplementation in fish induces metabolic shifts, such as alterations to gluconeogenesis and/or lipogenesis, modifying energy utilisation. Additionally, glycerol has been proposed to reduce protein catabolism, minimising nitrogen excretion and its environmental impact, but its influence on protein retention remains uncertain. Nevertheless, it is important to carefully consider the balance between feed palatability and these potential metabolic alterations when incorporating glycerol in aquafeeds. This review highlights the need for more studies to expand our understanding of glycerol metabolism in fish, since it does not seem to be metabolised by carnivorous species as much as omnivorous. Future research should explore the effects of glycerol supplementation on fish with different feeding habits and in developmental stages, as well as diverse environmental salinities and temperatures. Insight into the impact of impurities and the optimisation of glycerol inclusion in aquafeeds are recommended to support sustainable aquaculture practices and the utilisation of glycerol as a valuable resource. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic vascular wall disease and the most common pathological change in cardiovascular disease. Its pathogenesis is closely related to inflammation, oxidative stress, and lipid deposition. Bilirubin itself has biological activities such as antioxidant and anti-inflammatory effects, and has a protective effect on the cardiovascular system. This article summarizes the mechanism of bilirubin in the development of atherosclerosis and its research progress. [ABSTRACT FROM AUTHOR]

IntroductionFeeding frequency has been shown to affect growth and body composition of the host associated with gut microbiota. It remains unknown whether adjusting feeding frequency could effectively regulate both skeletal muscle development and whole-body lipid metabolism and thus affect carcass composition and feed conversion efficiency. Therefore, this study aimed to explore the effects of feeding frequency on muscle growth, fat deposition, cecal microbiota composition, and bile acid composition in finishing pigs.MethodsSixteen Sichuan-Tibetan black pigs, with an initial weight of 121.50 ± 1.60 kg, were divided into two groups and fed either two meals (M2) or four meals (M4) per day. The trial lasted 30 days. The muscle fiber characteristics, lipid metabolism in adipose tissue, and cecal microbiota and bile acid composition were determined.ResultsThe present study revealed that pigs fed four meals exhibited a lower feed-to-gain ratio, abdominal fat weight, and average backfat thickness (p < 0.05), as well as a higher loin eye area (p = 0.09) and myofiber diameter in the longissimus muscle than their counterparts. The mRNA expression of slow-twitch fiber and myogenesis-associated genes in the longissimus muscle was upregulated, while lipid metabolism-related genes in the backfat were downregulated in the M4 group compared to the M2 group (p < 0.05). The M4 pigs exhibited higher abundances of Firmicutes, Actinobacteriota, Bacillus, Clostridium_sensu_1, and Romboutsia, and lower abundances of Spirochaetota, Verrucomicrobiota, Treponema, and Muribaculaceae in the cecal content than the M2 pigs (p < 0.05). A higher feeding frequency increased the levels of primary bile acids and decreased the concentrations of taurine-conjugated bile acids in the cecal content of pigs (p < 0.05).ConclusionOur research suggested that the M4 feeding pattern, compared to the M2 pattern, promoted muscle growth and reduced fat deposition by enhancing fast- to slow-twitch fiber conversion and myogenesis in the muscle and repressing lipid metabolism in adipose tissue, associated with altered microbiota composition and bile acid profiles.

This study aimed to explore the mechanism by which total flavones of Abelmoschl manihot reduce intracellular lipid deposition in HK-2 cells (Human renal cortex proximal tubule epithelial cells) and thus reduce cell apoptosis. Palmitic acid was employed to induce intracellular lipid deposition. The cell proliferation activity was detected by the CCK-8 assay. The cell death status was evaluated by flow cytometry. The intracellular lipid deposition was observed by oil red O and BODIPY probe staining. The expression level of CD36 in HK-2 cells was determined by western blot. The results indicated that total flavones of A. manihot could inhibit the expression of CD36 in HK-2 cells in a dose-dependent manner and reduce lipid deposition. Consequently, total flavones of A. manihot protect HK-2 cells by reducing intracellular lipid deposition by inhibiting CD36-mediated fatty acid uptake.

ABSTRACT: The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 μM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.

ABSTRACT: Fatty liver disease in laying hens, characterized by excessive lipid accumulation in hepatocytes, poses significant challenges to poultry health and production efficiency. In this study, we investigated the therapeutic potential of epigallocatechin gallate (EGCG), a bioactive compound found in green tea, in mitigating oleic acid (OA)-induced hepatic steatosis in primary chicken hepatocytes. Treatment with EGCG effectively attenuated lipid deposition by downregulating lipid synthesis-related genes. Moreover, EGCG mitigated oxidative stress, inflammation, DNA damage, and apoptosis induced by OA, thereby preserving hepatocyte viability. Mechanistically, EGCG exerted its protective effects by modulating the p38 MAPK signaling pathway. Our findings suggest that EGCG holds promise as a therapeutic agent for managing fatty liver disease in poultry, offering insights into novel strategies for improving poultry health and production outcomes.

Fibroblast growth factor 1 (FGF1) regulates vertebrate cell growth, proliferation and differentiation, and energy metabolism. In this study, we cloned rainbow trout (Oncorhynchus mykiss) fgf1 and fgf1a, prepared their recombinant proteins (rFGF1 and rFGF1a), and described the molecular mechanisms by which they improve glycolipid metabolism in carnivorous fish. A 31-d feeding trial was conducted to investigate whether they could enhance glycolipid metabolism in rainbow trout on high-carbohydrate diets (HCD). A total of 720 rainbow trout (8.9 ± 0.5 g) were equally divided into 4 groups: the chow diet (CD) group injected with PBS, the HCD group injected with PBS, the HCD group injected with rFGF1 (400 ng/g body weight), and the HCD group injected with rFGF1a (400 ng/g body weight). The results showed that short-term HCD had a significant positive effect on the specific growth rate (SGR) of rainbow trout (P

Many studies have shown that long non-coding RNAs (lncRNAs) play key regulatory roles in various biological processes. However, the importance and molecular regulatory mechanisms of lncRNAs in donkey intramuscular fat deposition remain to be further investigated. In this study, we used published transcriptomic data from the longissimus dorsi muscle of Guangling donkeys to identify lncRNAs and obtained 196 novel lncRNAs. Compared with the coding genes, the novel lncRNAs and the known lncRNAs exhibited some typical features, such as shorter transcript length and smaller exons. A total of 272 coding genes and 52 lncRNAs were differentially expressed between the longissimus dorsi muscles of the low-fat and high-fat groups. The differentially expressed genes were found to be involved in various biological processes related to lipid metabolism. The potential target genes of differentially expressed lncRNAs were predicted by cis and trans. Functional analysis of lncRNA targets showed that some lncRNAs may act on potential target genes involved in lipid metabolism processes and regulate lipid deposition in the longissimus dorsi muscle. This study provides valuable information for further investigation of the molecular mechanisms of lipid deposition traits in donkeys, which may improve meat traits and facilitate the selection process of donkeys in future breeding. [ABSTRACT FROM AUTHOR]

AIM: This study aims to examine the ependymin-related protein 1 (EPDR1) expression in various tissues from wild-type C57BL/6 mice and type 2 diabetes (db/db) mice. The impact of EPDR1 on lipid accumulation in alpha mouse liver 12 (AML12) hepatocytes was also investigated. METHODS: Western blot was used to detect EPDR1 protein expression in the heart, liver, spleen, lung, kidney, gastrocnemius, brown adipose and brain tissues of C57BL/6 mice. Western blot and immunohistochemical (IHC) staining were also used to compare EPDR1 protein expression in the liver, gastrocnemius muscle, heart and kidney tissues of db/db and C57BL/6 mice. To develop an AML12 cell lipid deposition model, palmitic acid (PA)+oleic acid (OA) was used, and the cells were transfected with adenovirus overexpressing EPDR1 or treated with exogenous recombinant EPDR1 protein (rEPDR1). ELISA was conducted to determine intracellu-lar triglyceride (TG) content, and oil red O staining was employed to assess the effect of EPDR1 on lipid accumulation in AML12 cells. RESULTS: Western blot and IHC staining results revealed that EPDR1 was widely expressed in various tissues of wild-type mice, with the liver exhibiting the highest protein expression level. However, EPDR1 expression was down-regulated in the liver, gastrocnemius muscle, heart and kidney tissues in diabetic db/db mice compared with wild-type mice. Oil red O staining revealed that overexpression of EPDR1 in AML12 liver cells or rEPDR1 treatment led to reduced lipid accumulation. Furthermore, the TG content significantly decreased compared with the model group (P< 0. 05). CONCLUSION: EPDR1 is expressed in various tissues of wild-type mice, but showed diminished expression in the liver tissues of diabetic mice. Nevertheless, enhancing the expression of EPDR1 can aid in reducing lipid accumula tion in hepatocytes. These findings provide an experimental foundation for further exploration of the role of EPDR1 in the development of fatty liver in diabetic liver tissue. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of total flavones of Abelmoschus manihot (TFA) on renal glucose reabsorption. Methods A total of 24 C57BL/6 mice were assigned to control, high fat diet (HFD), and HFD+TFA groups using random number table method, 8 mice in each group. In vitro, HK2 cells were treated with palmitic acid (PA). The cells were divided into 3 groups: control group, PA group, and PA+TFA group. Oil red O staining was used to evaluate lipid accumulation. Immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting were used to evaluate glucose uptake and sodium glucose cotransporter 2 (SGLT2) expression. One-way analysis of variance (ANOVA) was used for comparison among groups. Results Massive lipid deposition in renal tubules was observed in HFD group, whereas no lipid deposition was found in the control group. Compared with HFD group, red-stained lipid droplets were significantly decreased in HFD+TFA group (P<0.001). The immunofluorescence results showed that SGLT2 protein in renal cortex tissue was dectected in three groups. Compared with the control group, SGLT2 expressions were significantly increased in HFD group and HFD+TFA group (P<0.05). However, SGLT2 expression in HFD+TFA group was lower than HFD group (P=0.049). The qRT-PCR results showed that SGLT2 mRNA in HFD group was significantly higher than that in the control group (P<0.001), while decreased after TFA intervention. In addition, treatment with TFA resulted in significant amelioration of lipid accumulation induced by PA in HK2 cells. Accompanied with improvement of lipid deposition, SGLT2 expression and glucose uptake were attenuated (P<0.05). Conclusions TFA can ameliorate renal lipid deposition, thereby inhibiting glucose reabsorption. Its renal protective effect may be related to its role in inhibiting SGLT2 expression. [ABSTRACT FROM AUTHOR]

Objective To study the influence of ANGPTL8 in lipopolysaccharide （LPS) ⁃induced hepatic lipid deposition. Methods Male wild⁃type（WT） and ANGPTL8 knockout mice at 6-8 weeks were used to induce sepsis models by intrabitoneal injection of LPS （10 mg/kg）. qPCR and immunofluorescence were used to detected the mRNA and protein expression of ANGPTL8 in liver tissue and HepG2 cells respectively: The contents of alanine aminotransferase （ALT), aspartate aminotransferase （AST） in serum and the triglyceride （TG） and malondialdehyde （MDA） in liver homogenate were detected by kits: the histopathological changes of liver tissue were analyzed through HE staining. Lipids accumulation in liver were detected by oil red O staining. The apoptosis of liver was determinated by TUNEL staining. RNA⁃seq was used to analyzing the differentially expressed genes in the liver tissue of WT and ANGPTL8 KO mice, and the qPCR and Western Blot were used to verify the differential expressed genes. Results The expression of ANGPTL8 in the liver was significantly upregulated at 48 hours after LPS stimulation. Compared with WT mice, the hepatic lipid deposition, steatosis, and apoptosis were significantly alleviated in liver of ANGPTL8 KO mice, the ALT and AST levels in serum and the TG and MDA content in liver homogenate of ANGPTL8 KO mice were also reduced significantly. The expression of caveolin⁃1（CAV1） in liver of ANGPTL8 KO mice was significantly higher than that of WT mice. Conclusions LPS promoted the expression and secretion of ANGPTL8 in liver tissue, and ANGPTL8 increased hepatic lipid deposition and peroxidation by inhibiting the expression of CAV1. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid‐induced triglyceride and cholesterol synthesis in HepG2cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high‐fat diet (HFD)‐induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein‐1 (SREBP1), fatty acid synthase (FASN), and stearoy‐CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a key factor for hepatocellular carcinoma (HCC) development. As a metabolic hepatic damage, there is still a lack of efficient therapy for NAFLD-HCC. Kurarinol (KUR) is a flavanone extracted from the root of Sophora flavescens, and exerts excellent hepatoprotective and lipid-lowering activities. But its potential on NAFLD-HCC still remains unclear, and thus was explored in our present study. Firstly, in vitro experiments revealed that KUR treatments markedly reduced lipid deposition and inflammatory response in hepatocytes under palmitate and oleic acid stimulation (PO) with decreased expression levels of fatty acid synthesis markers including fatty acid synthase (FASN), stearoyl-CoA desaturase-1 (SCD1) and sterol receptor element binding protein-1 (SREBP-1). Importantly, the proliferation of HCC cell lines was strongly limited by KUR in a dose-dependent manner. Of note, PO stimulation accelerated the proliferative capacity of HCC cells, whereas being significantly suppressed by KUR. Mechanistically, we found that epidermal growth factor receptor (EGFR) and its phosphorylation protein expression levels were highly down-regulated in hepatocytes and HCC cell lines under PO stimuli. More importantly, the functions of KUR to restrain lipid accumulation and HCC cell proliferation were diminished upon EGFR overexpression, confirming that EGFR suppression was necessary for KUR to treat NAFLD-HCC. Murine mouse models were finally established by the use of diethylnitrosamine (DEN) with high-fat/high-cholesterol diet (HFHC) feeding to determine the role of KUR in NAFLD-HCC. Oral gavage of KUR efficiently suppressed NAFLD-HCC formation in mice, as evidenced by the decreased tumor number and loading. KUR also ameliorated lipid accumulation, liver dysfunction, fibrosis and HCC cell proliferation in DEN/HFHC-challenged mice, along with decreased EGFR expression. Collectively, KUR may be an effective strategy for NAFLD-HCC prevention via EGFR signaling suppression.

Liver injury is closely related to poor outcomes in sepsis patients. Current studies indicate that sepsis is accompanied by metabolic disorders, especially those related to lipid metabolism. It is highly important to explore the mechanism of abnormal liver lipid metabolism during sepsis. As a key regulator of glucose and lipid metabolism, angiopoietin-like 8 (ANGPTL8) is involved in the regulation of multiple chronic metabolic diseases. In the present study, severe liver lipid deposition and lipid peroxidation were observed in the early stages of lipopolysaccharide (LPS) induced liver injury. LPS promotes the expression of ANGPTL8 both in vivo and in vitro. Knockout of Angptl8 reduced hepatic lipid accumulation and lipid peroxidation, improved fatty acid oxidation and liver function, and increased the survival rate of septic mice by activating the PGC1α/PPARα pathway. We also found that the expression of ANGPTL8 induced by LPS depends on TNF-α, and that inhibiting the TNF-α pathway reduces LPS-induced hepatic lipid deposition and lipid peroxidation. However, knocking out Angptl8 improved the survival rate of septic mice better than inhibiting the TNF-α pathway. Taken together, the results of our study suggest that ANGPTL8 functions as a novel cytokine in LPS-induced liver injury by suppressing the PGC1α/PPARα signaling pathway. Therefore, targeting ANGPTL8 to improve liver lipid metabolism represents an attractive strategy for the management of sepsis patients.

Abstract Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate (HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level. Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate (SA) and sodium butyrate (SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC (9% starch), HC (18% starch), HCSA (18% starch; 2 g/kg SA), HCSB (18% starch; 2 g/kg SB), and HCSASB (18% starch; 1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d. Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy (ATG101, LC3B and TFEB), promoting lipolysis (CPT1α, HSL and AMPKα), and inhibiting adipogenesis (FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver (CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors (IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate (Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition. Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition; and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.

Introduction: Growing evidence has shown the correlation between periodontitis and atherosclerosis, while our knowledge on the pathogenesis of periodontitis-promoting atherosclerosis is far from sufficient. Objectives: Illuminate the pathogenic effects of Fusobacterium nucleatum (F. nucleatum) on intracellular lipid deposition in THP-1-derived macrophages and elucidate the underlying pathogenic mechanism of how F. nucleatum promoting atherosclerosis. Methods and results: F. nucleatum was frequently detected in different kinds of atherosclerotic plaques and its abundance was positively correlated with the proportion of macrophages. In vitro assays showed F. nucleatum could adhere to and invade THP-1 cells, and survive continuously in macrophages for 24 h. F. nucleatum stimulation alone could significantly promote cellular inflammation, lipid uptake and inhibit lipid outflow. The dynamic gene expression of THP-1 cells demonstrated that F. nucleatum could time-serially induce the over-expression of multiple inflammatory related genes and activate NF-κB, MAPK and PI3K-AKT signaling pathways. The exoprotein of F. nucleatum, D-galactose-binding protein (Gbp), acted as one of the main pathogenic proteins to interact with the Cyclophilin A (CypA) of THP-1 cells and induced the activation of the NF- κB, MAPK and PI3K-AKT signaling pathways. Furthermore, use of six candidate drugs targeting to the key proteins in NF- κB, MAPK and PI3K-AKT pathways could dramatically decrease F. nucleatum induced inflammation and lipid deposition in THP-1 cells. Conclusions: This study suggests that the periodontal pathogen F. nucleatum can activate macrophage PI3K-AKT/MAPK/NF-κB signal pathways, promotes inflammation, enhances cholesterol uptake, reduces lipid excretion, and promotes lipid deposition, which may be one of its main strategies promoting the development of atherosclerosis.

Lipid accumulation and oxidative stress, which could be improved by autophagy, are the “hits” of metabolic-associated fatty liver disease (MAFLD). Ganoderma lucidum spore powder (GLSP) has the effect of improving liver function. However, there are few reports about its effects on and mechanisms impacting MAFLD alleviation. This study investigated the effect of GLSP on hepatic lipid accumulation and oxidative stress and explored the role that autophagy played in this effect. The results showed that GLSP effectively reduced lipid accumulation and activated autophagy in the livers of mice with high-fat-diet-induced disease and palmitic acid-induced hepatocytes. GLSP reduced the lipid accumulation by reducing lipogenesis and promoting lipid oxidation in HepG2 cells. It decreased the production of ROS, increased the activity of SOD and CAT, and improved the mitochondrial membrane potential via the Keap1/Nrf2 pathway. The alleviating effects of GLSP on the lipid accumulation and oxidative stress was reversed by 3-methyladenine (3-MA), an autophagy inhibitor. GLSP activated autophagy via the AMPK pathway in HepG2 cells. In conclusion, GLSP could attenuate MAFLD by the improvement of lipid accumulation and oxidative stress via autophagy. This paper is the first to report the improvement of MAFLD through autophagy promotion. It will shed novel light on the discovery of therapeutic strategies targeting autophagy for MAFLD.

Background: Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate (HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level. Method: Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate (SA) and sodium butyrate (SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC (9% starch), HC (18% starch), HCSA (18% starch; 2 g/kg SA), HCSB (18% starch; 2 g/kg SB), and HCSASB (18% starch; 1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d. Results: We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy (ATG101, LC3B and TFEB), promoting lipolysis (CPT1α, HSL and AMPKα), and inhibiting adipogenesis (FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver (CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors (IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate (Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition. Conclusions: In conclusion, dietary SA and SB can reduce hepatic lipid deposition; and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA. [ABSTRACT FROM AUTHOR]

1. Two experiments were conducted to measure the response of growing turkeys to dietary protein content. In the first, 960 sexed British United Turkey (BUT 6) poults were used to measure the response to balanced protein from 3 to 6 weeks of age. In the second, 1440 sexed BUT and Hybrid Converter poults were raised from 14 to 17 weeks. 2. In both experiments, six levels of dietary protein were fed, with feed intake, body and feather weight gain and changes in body composition measured. The levels of protein chosen ranged from 0.53 to 1.2 of the Aviagen requirements for growing turkeys. 3. In the first experiment, six poults were sampled from each sex at the start of the experiment for carcass analysis, and four were sampled from each strain and sex in the second. At the end of each experiment, eight poults from each treatment were sampled. Body composition analyses were made on individual defeathered birds. 4. Weight gain increased linearly with protein intake in the early period and exponentially in the later period. In both periods, feed intake decreased as protein content reduced. 5. In the early period, body lipid content increased from 20.2 to 41.5 g/kg body weight, as dietary protein content decreased, but there was no change in the later period. Efficiency of utilisation of dietary protein declined linearly with an increase in dietary protein content, from 0.87 to 0.46 g/g in the first, and from 0.43 to 0.27 g/g in the later period. 6. The inability of the growing turkey to increase feed intake on marginally limiting feeds may have been due to a genetic constraints to store excess energy consumed as body lipid, resulting in the observed decrease in feed intake as dietary protein content is reduced. [ABSTRACT FROM AUTHOR]

Simple Summary: Succinate is an important product of the fermentative metabolism of dietary fiber, and similar to propionate, high levels of succinate in the gut modulate the body's inflammatory response, glucose tolerance, and lipid metabolism. Our study showed that the addition of 1% succinate to pig diets promoted growth and fat deposition capacity without affecting feed intake, remodeled the fatty acid content of the longissimus dorsi muscle, and consequently improved meat quality. Further, we isolated and cultured primary porcine preadipocytes. The results showed that succinate increased the expression of genes related to adipogenic differentiation while decreasing the levels of genes related to lipolysis and promoting the formation of cellular lipid droplets. Mechanistically, dietary supplementation with succinate increases succinylation modification in adipose tissue to promote facilitated lipogenesis. This suggests that it is feasible and important to improve fatty acids and meat quality in porcine muscle through dietary succinate supplementation. Succinate, one of the intermediates of the tricarboxylic acid cycle, is now recognized to play a role in a broad range of physiological and pathophysiological settings, but its role in adipogenesis is unclear. Our study used Bama miniature pigs as a model to explore the effects of succinate on performance, meat quality, and fat formation. The results showed that adding 1% succinate significantly increased the average daily gain, feed/gain ratio, eye muscle area, and body fat content (p < 0.05), but had no effect on feed intake. Further meat quality analysis showed that succinate increased the marbling score and intramuscular fat content of longissimus dorsi muscle (LM), while decreasing the shear force and the cross-sectional area of LM (p < 0.05). Metabolomics analysis of LM revealed that succinate reshaped levels of fatty acids, triglycerides, glycerophospholipids, and sphingolipids in LM. Succinate promotes adipogenic differentiation in porcine primary preadipocytes. Finally, dietary succinate supplementation increased succinylation modification rather than acetylation modification in the adipose tissue pool. This study elucidated the effects of succinate on the growth and meat quality of pigs and its mechanism of action and provided a reference for the role of succinate in the nutrition and metabolism of pigs. [ABSTRACT FROM AUTHOR]

Lifestyle intervention encompassing nutrition and physical activity are effective strategies to prevent progressive lipid deposition in the liver. This study aimed to explore the effect of dietary change, and/or high-intensity interval training (HIIT) on hepatic lipid accumulation in high fat diet (HFD)-induced obese rats. We divided lean rats into lean control (LC) or HIIT groups (LH), and obese rats into obese normal chow diet (ND) control (ONC) or HIIT groups (ONH) and obese HFD control (OHC) or HIIT groups (OHH). We found that dietary or HIIT intervention significantly decreased body weight and the risk of dyslipidemia, prevented hepatic lipid accumulation. HIIT significantly improved mitochondrial fatty acid oxidation through upregulating mitochondrial enzyme activities, mitochondrial function and AMPK/PPARα/CPT1α pathway, as well as inhibiting hepatic de novo lipogenesis in obese HFD rats. These findings indicate that dietary alone or HIIT intervention powerfully improve intrahepatic storage of fat in diet induced obese rats. [ABSTRACT FROM AUTHOR]

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