Expression Of Lipid Metabolism-related Genes Research Articles

Network pharmacology combined with molecular docking and molecular dynamic simulation to reveal the potential mechanism of lentinan ameliorating hyperlipidemia

Hyperlipidemia is closely related to multiple diseases and is characterized by abnormal serum lipid profiles. The biological function of lentinan in mice and rats was studied, but the mechanism of its lipid-lowering effect was not completely clear. In this study, network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the potential mechanism of its lipid-lowering effect and high-fat diet (HFD) mice was used to confirm the predicted mechanism. Our results indicated that lentinan could ameliorate hyperlipidemia by regulating peroxisome proliferator-activated receptors (PPARs), sterol response element-binding protein-1 (SREBP1), and nuclear factor kappa-B (NF-κB) in the hepatic tissues of mices. Further animal experiment showed that lentinan could regulate the mRNA expressions of lipid metabolism-related genes, such as PPARα, PPARδ, PPARγ, cluster of differentiation 36 (CD36) and SREBP-1c. Moreover, lentinan supplementation could reduce the expressions of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide sythase (iNOS). In cell model, lentinan also could inhibit oleic acid-induced lipid droplet formation and the expressions of lipid metabolism-related genes and reduced inflammatory factor expressions in HepG2 cells, which further approved the results of animal experiment. Taken together, our results suggest that lentinan can ameliorate hyperlipidemia via regulating lipid metabolism-related gene expressions and reduce obesity-induced inflammatory response.

Dietary lipid supplementation alleviated the impacts of polystyrene nanoplastic exposure in Litopenaeus vannamei

The widespread occurrence of nanoplastic (NP) pollution in the environment is a growing concern, and its presence poses a potential threat to cultured aquatic animals. Previously, we found that NPs can significantly affect the lipid metabolism of shrimp. However, relevant reports about the effects of increasing dietary lipid levels on NP toxicity are lacking. Therefore, we explored the effects of dietary supplementation with different lipid levels on the growth and lipid metabolism of Pacific white shrimp (Litopenaeus vannamei). We cultured L. vannamei at three dietary lipid levels (3 %, 6 %, and 9 %) and three NP concentrations (0, 1, and 3 mg/L) for 2 months. We evaluated the effects of lipid levels on growth indexes, hepatopancreas morphological structure, lipid metabolism-related enzyme activity, and gene expression of the shrimp. The results showed that as lipid intake increased, the survival rate, body weight growth rate, and hepatosomatic ratio of the shrimp increased while the feed conversion rate decreased. Additionally, the crude protein and crude lipid contents increased, whereas the moisture and ash contents did not change much. We found that the morphological structure of the hepatopancreas was seriously damaged in the 3 mg/L NPs and 3 % dietary lipid group. Finally, lipid metabolism-related enzyme activities and gene expression levels increased with increased dietary lipid levels. Together, these results suggest that increasing dietary lipid content can improve shrimp growth and alleviate lipid metabolism disorders caused by NPs. This study is the first to show that nutrition regulation can alleviate the toxicity of NPs, and it provides a theoretical basis for the green and healthy culture of L. vannamei.

Effects of grape seed procyanidins on the lipid metabolism of growing-finishing pigs based on transcriptomics and metabolomics analyses

This study investigated how lipid metabolism in the longissimus thoracis is influenced by the diet supplemented with grape seed procyanidins (GSPs) in growing-finishing pigs. Forty-eight crossbred pigs were randomly assigned to four groups, each receiving a basal diet, or basal diet added with 150, 200, and 250 mg/kg GSPs. Transcriptomics and metabolomics were employed to explore differential gene and metabolite regulation. The expression of key lipid metabolism-related genes was tested via qRT-PCR, and the lipid and fatty acid composition of the longissimus thoracis were determined. Dietary GSPs at different concentrations upregulated lipoprotein lipase (LPL), which is involved in lipolysis, and significantly increased the mRNA expression levels of carnitine palmitoyltransferase-1B (CPT1B) and cluster of differentiation 36 (CD36), implicated in transmembrane transport of fatty acids. Dietary supplementation of GSPs at 200 or 250 mg/kg markedly reduced total cholesterol and triglyceride content in longissimus thoracis. Dietary GSPs significantly decreased the contents of low-density lipoprotein cholesterol and saturated fatty acids, while increasing unsaturated fatty acids. In conclusion, GSPs may regulate lipid metabolism, reducing cholesterol level, and improving fatty acid composition in the longissimus thoracis of growing-finishing pigs. Our findings provide evidence for the beneficial effects of GSPs as pig feed additives for improving lipid composition.

HMGB2 Promotes De Novo Lipogenesis to Accelerate Hepatocyte Proliferation During Liver Regeneration.

Liver regeneration is a well-orchestrated compensatory process that is regulated by multiple factors. We recently reported the importance of the chromatin protein, a high-mobility group box 2 (HMGB2) in mouse liver regeneration. However, the molecular mechanism remains unclear. In this study, we aimed to study how HMGB2 regulates hepatocyte proliferation during liver regeneration. Seventy-percent partial hepatectomy (PHx) was performed in wild-type (WT) and HMGB2-knockout (KO) mice, and the liver tissues were used for microarray, immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blotting analyses. In the WT mice, HMGB2-positive hepatocytes colocalized with cell proliferation markers. In the HMGB2-KO mice, hepatocyte proliferation was significantly decreased. Oil Red O staining revealed the transient accumulation of lipid droplets at 12-24 hr after PHx in the WT mouse livers. In contrast, decreased amount of lipid droplets were found in HMGB2-KO mouse livers, and it was preserved until 36 hr. The microarray, immunohistochemistry, and qPCR results demonstrated that the expression of lipid metabolism-related genes was significantly decreased in the HMGB2-KO mouse livers. The in vitro experiments demonstrated that a decrease in the amount of lipid droplets correlated with decreased cell proliferation activity in HMGB2-knockdown cells. HMGB2 promotes de novo lipogenesis to accelerate hepatocyte proliferation during liver regeneration.

High protein-low carbohydrate diet can improve hypoxia tolerance of triploid rainbow trout (Oncorhynchus mykiss): Effects on physiological and metabolic responses to acute hypoxia

Triploid rainbow trout is a hypoxia-sensitive fish species, and is susceptible to death in summer with high water temperature induced acute hypoxia. The study was conducted to evaluate the effect of high protein diet and high carbohydrate diet on hypoxic tolerance of triploid rainbow trout. Two isolipidic and isoenergetic diets with low protein-high carbohydrate level (LPHC) and high protein-low carbohydrate level (HPLC) were specifically formulated. After the feeding trial with 80 days, two group fish were treated with acute hypoxic challenge. Plasma biochemical parameters, hepatic anti-stress, antioxidant and immune related genes expression, and hepatic glucose, lipid, protein and amino acid metabolism related genes expression were then analyzed. The results showed that compared with HPLC diet, LPHC diet could result in excessive plasma levels of alanine aminotransferase (ALT; 36.3 VS 14.0 U/L), aspartate aminotransferase (AST; 978 VS 366 U/L), alkaline phosphatase (ALP; 374 VS 204 U/L), creatine phosphokinase (CPK; 7538 VS 4937 U/L) and lactate dehydrogenase (LDH; 940 VS 451 U/L). In addition, HPLC diet could remodel metabolism of glucose, lipid and protein based on the mRNA expression levels of the genes regulating glycometabolism, lipometabolism, and protein and amino acids metabolism. HPLC diet also enhanced the mRNA expression levels of the genes regulating anti-stress (HSP70, HIF-1a and HIF-2a), antioxidant (Nrf2, SOD, CAT, GPx and HO-1) and immune (IFN-γ, IL-1β, TNF-α and IL-8). In total, LPHC diet could aggravate hypoxic stress of triploid rainbow trout, while HPLC diet could improve fish hypoxic tolerance.

Marine Fish Oil Replacement with Lard or Basa Fish (Pangasius bocourti) Offal Oil in the Diet of Tiger Puffer (Takifugu rubripes): Effects on Growth Performance, Body Composition, and Flesh Quality.

Lard (LD) and Basa fish offal oil (BFO) have similar fatty acid profiles, both containing high contents of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA). The present study aimed to investigate the efficacy of partial or complete replacement of marine fish oil (MFO, herring oil) by LD or BFO in the diets of tiger puffer. The control diet contained 49.1% crude protein and 9.28% crude lipid content including 6% added MFO. In other diets, 1/3, 2/3, and 3/3 of the added MFO was replaced by LD or BFO, respectively. Each diet was fed to triplicate tanks of juvenile fish (initial body weight, 13.88 g). A 46-day feeding trial was conducted in a flow-through seawater system. Each diet was fed to triplicate 200-L rectangular polyethylene tanks, each of which was stocked with 30 fish. Fish were fed to satiation three times a day. The complete replacement of added MFO (replacing 65% of the total crude lipid) had no adverse effects on fish growth performance in terms of survival (>94%), weight gain (360-398%), feed intake (2.37-3.04%), feed conversion ratio (0.84-1.02), and somatic indices. The dietary LD or BFO supplementation also had marginal effects on fish body proximate composition, biochemical parameters, muscle texture, and water-holding ability, as well as the hepatic expression of lipid metabolism-related genes. Partial (2/3) replacement of added MFO by LD or BFO did not significantly reduce the muscle n-3 LC-PUFA content, indicating the n-3 LC-PUFA sparing effects of SFA and MUFA in LD and BFO. In general, dietary LD or BFO reduced the peroxidation level and led to significant changes in the muscle volatile flavor compound profile, which were probably attributed to the change in fatty acid composition. The results of this study evidenced that LD and BFO are good potential lipid sources for tiger puffer feeds.

Dietary Bacillus species modulate lipid metabolism-related parameters, growth, water quality, and bacterial load in Nile tilapia (Oreochromis niloticus )

This study examined the impact of supplementing Bacillus spp. mixtures at concentrations of 0.2 g/kg (PRO-0.2) and 0.5 g/kg (PRO-0.5) on Nile tilapia (Oreochromis niloticus) for 90 days. Fish groups receiving PRO-0.2 and PRO-0.5 exhibited significantly lower water ammonia levels than the control group, in linear and quadratic patterns. Furthermore, their length and weight increased exponentially over time, peaking at the end of the experiment. After 90 days, the PRO-0.5 group displayed the highest mean weight gain. Additionally, both the PRO-0.2 and PRO-0.5 groups had the lowest food conversion ratios and highest protein efficiency ratios in a linear pattern. They also showed improved liver function, as indicated by lower levels of liver enzyme (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) compared to the control group. In terms of the lipid profile, the PRO-0.2 and PRO-0.5 groups had significantly lower serum levels of low-density lipoprotein, triglycerides, in linear and quadratic patterns, and cholesterol compared to the control group, with no significant differences in cholesterol levels. High-density lipoprotein increased significantly in both PRO-0.2 and PRO-0.5 groups after 90 days, following a linear pattern. Hepatic alkaline phosphatase levels decreased in both the PRO-0.2 and PRO-0.5 groups, following a significant linear pattern over time. After 30 days, the expression of hepatic fatty acid binding protein 3 (fabp3) significantly decreased in the PRO-0.5 group. Intestinal cluster of differentiation 36 (cd36) and fabp3 expression markedly increased, with cd36 showing the greatest rise. After 90 days, hepatic cd36 expression became prominent in both PRO-0.2 and PRO-0.5 groups. Expression of fas was significantly downregulated in both the PRO-0.2 and PRO-0.5 groups. Notably, hepatic lipoprotein lipase (lpl) expression significantly increased in the supplementation groups after 30 days but decreased significantly after 90 days. Overall, this study highlights the positive impact of dietary mixtures of Bacillus spp. on various aspects, including water quality, growth performance, feed utilization, survivability, expression of lipid metabolism-related genes, lipid profile, body composition, and bacterial load in both water and fish bodies.

Evaluation of carcass traits, meat quality and the expression of lipid metabolism-related genes in different slaughter ages and muscles of Taihang black goats.

This study was conducted to investigate the effect of slaughter age on carcass traits, meat quality, and the relative mRNA levels of lipid metabolism-related genes in different muscles of Taihang black goats. In this study, the triceps brachii (TB), longissimus dorsi (LD) and gluteus (GL) muscles of 15 grazing Taihang black goats slaughtered at the age of 2, 3, and 4(designated as 2-year-old, 3-year-old, and 4-year-old, respectively) were collected. The differences in carcass shape, meat quality, amino acid composition and lipid metabolism gene expression among Taihang black goats of different ages and from different plant parts were compared. Compared with goats at other ages, goats slaughtered at the age of 4 had greater live and carcass weights, meat weights, bone weights and skin areas (P<0.05). LD in the 4-years-old had the lowest cooking loss and moisture content. The content of crude protein in 2-year-old was significantly greater than that in the other muscles. The highest fat content was in LD, followed by TB, for goats slaughtered at the age of 4. Eight out of 9 essential amino acids had higher content in the TB compared with other muscles, regardless of age. The total essential amino acid content was highest in the 4-year-old and lowest in the GL muscle at the age of 3. The SREBP-1c and ATGL genes were significantly more abundant in the TB muscle than in the other muscles for goats slaughtered at the age of 2. At the the age of 4, the ATGL and PPARγ genes were significantly more abundant in the GL than in the LD, while the FAS genes were significantly less abundant in the GL than in the other muscles. Similarly, compared with those in goats of other ages, the relative mRNA expression levels of the FAS and H-FABP genes in goats slaughtered at the age of 4 were the highest, and the relative mRNA expression of the PPARγ gene was the lowest (P<0.05). The relative mRNA expression of the H-FABP and FAS genes was positively correlated with the intramuscular fat (IMF) content, while the relative mRNA expression levels of the PPARγ and ATGL genes was negatively correlated with the IMF content. Overall, a better nutritional value was obtained for TB from 4-year-old goats, in which the total essential amino acid and fat contents were greater than those of other muscles. The comprehensive action of lipid metabolism genes was consistent with that of the IMF content, among which the FAS, H-FABP, PPARγ and ATGL genes had positive and negative effects on the process of IMF deposition in Taihang black goats.

Effects of microcystin-LR on immune function, lipid metabolism and intestinal microbial structure in Eriocheir sinensis

To investigate the potential toxic mechanism of Microcystin-LR (MC-LR) on juvenile Eriocheir sinensis (E. sinensis), a toxicity test was conducted by injecting MC-LR into the 3rd pereiopod. Following injection, we evaluated alterations in immune response biomarkers, antioxidant status, lipid metabolism-related genes expression, and intestinal microbiota composition in the hepatopancreas and intestinal tissues of E. sinensis. The results of immune response showed that after injection of MC-LR, the serum complement C3 level in E. sinensis significantly decreased at 48 hours (P < 0.05), whereas complement C4 level increased considerably from 12 to 96 hours (P < 0.01). The phenoloxidase system (PO) showed an increasing trend from 6 to 96 hours (P < 0.05 or P < 0.01). The levels of TNF-α, IL-6 significantly increased at 6 and 12 hours (P < 0.05 or P < 0.01). Gene expression analysis showed that FASN gene in the hepatopancreatic tissue displayed a higher expression at both 6 and 12 hours post-exposure (P < 0.01), while ALDH and ACAA2 gene exhibited a consistent downward trend from 6 to 48 hours (P < 0.05), Additionally, the mRNA levels of MECR and ACSL demonstrated a pattern of initial downregulation, followed by an upregulation, and subsequent downregulation. The antioxidant status results revealed that the levels GSH and CAT increased first and then decreased, while the activity of SOD decreased first and then increased. Meanwhile, the MDA content showed an increasing trend. 16 S rDNA analysis showed that the intestinal microbial diversity in MC-LR treatment group was significantly higher relative to the control group (P < 0.01). Compared with the control group, the MC-LR group had a significantly higher relative abundance of Proteobacteria, Fusobacteria, and Actinobacteria (P < 0.05) and a significantly lower relative abundance of Firmicutes (P < 0.01). At genus level, the relative abundance of Acinnetobacter, Flavobacterium, Acidovorax, Paracoccus, Cloacibacterium, Gemmobacter, Aeromonas, and Dechloromonas in the intestine of MC-LR-treated group was significantly increased relative to the control group (P < 0.05 or P < 0.01), but the relative abundance of Lachnospiraceae_NK4A136_group was significantly decreased (P < 0.01). The results of the study demonstrated that MC-LR could induced oxidative stress, hepatopancreas tissue damage, and intestinal microbial imbalance in E. sinensis.

Effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks.

Exogenous supplementation of guanidinoacetic acid can mechanistically regulate the energy distribution in muscle cells. This study aimed to investigate the effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. We randomly divided 480 42 days-old female Jiaji ducks into four groups with six replicates and 20 ducks for each replicate. The control group was fed the basal diet, and the experimental groups were fed the basal diet with 400, 600, and 800 mg/kg (GA400, GA600, and GA800) guanidinoacetic acid, respectively. Compared with the control group, (1) the total cholesterol (p = 0.0262), triglycerides (p = 0.0357), malondialdehyde (p = 0.0452) contents were lower in GA400, GA600 and GA800 in the liver; (2) the total cholesterol (p = 0.0365), triglycerides (p = 0.0459), and malondialdehyde (p = 0.0326) contents in breast muscle were decreased in GA400, GA600 and GA800; (3) the high density lipoprotein (p = 0.0356) and apolipoprotein-A1 (p = 0.0125) contents were increased in GA600 in the liver; (4) the apolipoprotein-A1 contents (p = 0.0489) in breast muscle were higher in GA600 and GA800; (5) the lipoprotein lipase contents (p = 0.0325) in the liver were higher in GA600 and GA800; (6) the malate dehydrogenase contents (p = 0.0269) in breast muscle were lower in GA400, GA600, and GA800; (7) the insulin induced gene 1 (p = 0.0326), fatty acid transport protein 1 (p = 0.0412), and lipoprotein lipase (p = 0.0235) relative expression were higher in GA400, GA600, and GA800 in the liver; (8) the insulin induced gene 1 (p = 0.0269), fatty acid transport protein 1 (p = 0.0234), and lipoprotein lipase (p = 0.0425) relative expression were increased in GA400, GA600, and GA800 in breast muscle. In this study, the optimum dosage of 600 mg/kg guanidinoacetic acid improved the liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks.

Modulation Mechanism of Wuniuzao Dark Tea Polysaccharide on Lipid Metabolism in Hyperlipidemic Mice Induced by High-Fat Diet.

The aim of this study was to investigate the functional mechanism of Wuniuzao dark tea polysaccharide (WDTP) that protect against hyperlipidemia in mice induced by high-fat diet. WDTP was extracted by hot water, isolated and purified by DEAE-52 chromatography and characterized by high-performance liquid chromatograph (HPLC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). Different doses (200 or 800mg/kg/day) of WDTP were orally administered to mice induced by high-fat diet to evaluate the mechanism of WDTP regulating lipid metabolism. And these results showed that average molecular weight of WDTP was nearly 63,869 Da. And WDTP intervention significantly reduced body weight, lipid accumulation, and modulated blood lipid levels. The mechanism of WDTP ameliorating lipid metabolism was associated with regulating the expression of lipid metabolism-related genes and serum exosomes miR-19b-3p, and modulating the community structure of gut microbiota in mice.

Probiotic yogurt regulates gut microbiota homeostasis and alleviates hepatic steatosis and liver injury induced by high-fat diet in golden hamsters.

This study aimed to investigate the beneficial effects of probiotic yogurt on lipid metabolism and gut microbiota in metabolic-related fatty liver disease (MAFLD) golden hamsters fed on a high-fat diet (HFD). The results demonstrated that probiotic yogurt significantly reversed the adverse effects caused by HFD, such as body and liver weight gain, liver steatosis and damage, sterol deposition, and oxidative stress after 8 weeks of intervention. qRT-PCR analysis showed that golden hamsters fed HFD had upregulated genes related to adipogenesis, increased free fatty acid infiltration, and downregulated genes related to lipolysis and very low-density lipoprotein secretion. Probiotic yogurt supplements significantly inhibited HFD-induced changes in the expression of lipid metabolism-related genes. Furthermore, 16S rRNA gene sequencing of the intestinal content microbiota suggested that probiotic yogurt changed the diversity and composition of the gut microbiota in HFD-fed hamsters. Probiotic yogurt decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio, and bacteria involved in lipid metabolism, whereas it increased the relative abundance of short-chain fatty acids producing bacteria in HFD-fed hamsters. Predictive functional analysis of the microbial community showed that probiotic yogurt-modified genes involved in LPS biosynthesis and lipid metabolism. In summary, these findings support the possibility that probiotic yogurt significantly improves HFD-induced metabolic disorders through modulating intestinal microflora and lipid metabolism and effectively regulating the occurrence and development of MAFLD. Therefore, probiotic yogurt supplementation may serve as an effective nutrition strategy for the treatment of patients with MAFLD clinically.

Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

Effect of DHCR7 on adipocyte differentiation in goats

Cholesterol is regarded as a signaling molecule in regulating the metabolism and function of fat cells, in which 7-Dehydrocholesterol reductase (DHCR7) is a key enzyme that catalyzes the conversion of 7-dehydrocholesterol to cholesterol, however, the exact function of DHCR7 in goat adipocytes remains unknown. Here, the effect of DHCR7 on the formation of subcutaneous and intramuscular fat in goats was investigated in vitro, and the result indicated that the mRNA level of DHCR7 showed a gradual downward trend in subcutaneous adipogenesis, but an opposite trend in intramuscular adipogenesis. In the process of subcutaneous preadipocytes differentiation, overexpression of DHCR7 inhibited the expression of adipocytes differentiation marker genes (CEBP/α, CEBP/β, SREBP1 and AP2), lipid metabolism-related genes (AGPAT6, FASN, SCD1 and LPL), and the lipid accumulation. However, in intramuscular preadipocyte differentiation, DHCR7 overexpression showed a promoting effect on adipocyte differentiation marker genes (CEBP/α, CEBP/β, PPARγ and SREBP1) and lipid metabolism-related genes (GPAM, AGPAT6, DGAT1 and SCD1) expression, and on lipid accumulation. In summary, our work demonstrated that DHCR7 played an important role in regulating adipogenic differentiation and lipid metabolism in preadipocytes in goats, which is of great significance for uncovering the underlying molecular mechanism of adipocyte differentiation and improving goat meat quality.

Modulation of lipid metabolism by oyster peptides in mice with high-fat diet-induced obesity

Oysters (Crassostrea gigas) are rich in proteins and a source of valuable peptides. Previous studies have revealed that oral administration of oyster peptides (OP) obtained by simulating gastrointestinal digestion reduced the weight of mice. However, the underlying regulatory mechanisms are unclear. We speculate that OP may be able to reduce fatty acid absorption by inhibiting pancreatic lipase activity. Therefore, we investigated the regulatory effects of OP on lipid metabolism in mice with high-fat diet-induced obesity. The body weight (BW), fat weight, lipid parameters, lipid metabolism-related gene expression, and serum lipid profiles were determined by MS-based lipidomics. Daily supplementation with 500 mg of OP/kg BW in obese mice reduced their BW gain and organ weights, improved dyslipidemia, and downregulated the genes expression of encoding proteins involved in fatty acid uptake, including acetyl coenzyme A carboxylase 1 (Acc1), fatty acid synthase (Fas), and sterol regulatory element binding protein 1c (Srebp-1c). Moreover, administration of OP resulted in significant changes in the lipid profile of mice. We screened 129 differential metabolites to identify biomarkers for OP intervention and analyzed the effects of OP on the metabolism of sphingolipids, glycerophospholipids, linoleic acid, and α-linolenic acid. In summary, OP can improve obesity-induced lipid metabolism dysfunctions by inhibiting enzyme activity and regulating fatty acid uptake.

Validating the Health Benefits of Coffee Berry Pulp Extracts in Mice with High-Fat Diet-Induced Obesity and Diabetes.

The effects of coffee (Coffea arabica L.) berry pulp extracts (CBP extracts) on the improvement of diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) were evaluated using various in vitro antioxidant activity assays and through a high-fat diet-induced mild diabetic obese mouse model. After an 84-day oral administration of CBP extracts (400-100 mg/kg), bioactivities were evaluated. The in vitro analysis showed the highest DPPH● scavenging activity of 73.10 ± 4.27%, ABTS● scavenging activity of 41.18 ± 1.14%, and SOD activity of 56.24 ± 2.81%, at a CBP extract concentration of 1000 µg/mL. The in vivo analysis of the CBP extracts showed favorable and dose-dependent anti-obesity, anti-diabetic, NAFLD, nephropathy, and hyperlipidemia refinement effects through hepatic glucose enzyme activity, 5'-AMP-activated protein kinase (AMPK) up-regulation, antioxidant activity, lipid metabolism-related gene expression, and pancreatic lipid digestion enzyme modulatory activities. This study shows that an appropriate oral dosage of CBP extracts could function as a potent herbal formulation for a refinement agent or medicinal food ingredient to control type 2 diabetes and related complications.

Lipoproteins in Negative Feedback with Alpha-1 Antitrypsin.

Alpha-1 antitrypsin deficiency patients (AATD) have lower risk of myocardial infarction, a cardiovascular disease that is related to increased remnant cholesterol levels, but not to low-density lipoprotein (LDL) levels. However, when AAT is knocked out in mice (AAT-KO), inflammatory-related, cholesterol metabolism-related, and lipid metabolism-related gene expression in mouse liver was increased, and these data support previous evidence from clinic patients and from a small clinical trial that AAT is in negative feedback regulation with LDL. Herein is a brief summary to examine the roles of AAT in these overlapping pathways.

The anti-hyperlipidemic effects of Poria cocos (Schw.) Wolf extract: Modulating cholesterol homeostasis in hepatocytes via PPARα pathway

Ethnopharmacological relevancePoria cocos (Schw.) Wolf (Polyporaceae, P.cocos), which is born on the pine root, has a history of more than two thousand years of medicine in China. P.cocos was first recorded in the Shennong's Herbal Classic, studies have proved its lipid-lowering effect. Aim of studyThe aim of study was to investigate the underlying mechanism of P.cocos extract on hyperlipidemia. Materials and methodsMale Sprague-Dawley (SD) rats aged 9–12 weeks were intraperitoneally (IP) injected with Triton-WR 1339 to establish an acute hyperlipidemia model. At 0 h and 20 h after the model was established, low and high doses of P.cocos extract or simvastatin were given twice. After 48 h, the rats were sacrificed, and liver and serum samples were collected for analysis. The cell model was constructed by treating L02 cells with 1% fat emulsion-10% FBS–RPMI 1640 medium for 48 h. At the same time, low and high doses of P.cocos extract and simvastatin were administered. Oil red O staining was used to evaluate the lipid accumulation in the cells, and H&E staining was used to evaluate the liver lesions of rats. Real-time quantitative PCR and western blotting were used to detect the expressions of lipid metabolism-related genes. ResultsP.cocos extract relieved lipid accumulation in vitro and alleviated hyperlipidemia in vivo. Both gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα) were shown to be up-regulated by P.cocos extract. Additionally, P.cocos extract down-regulated the expressions of fatty acid synthesis-related genes sterol regulatory element-binding protein-1 (SREBP-1), Acetyl-CoA Carboxylase 1 (ACC1) and fatty acid synthase (FAS), while up-regulated the expressions of cholesterol metabolism-related genes liver X receptor-α (LXRα), ATP-binding cassette transporter A1 (ABCA1), cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein receptor (LDLR), which were reversed by the treatment with the PPARα inhibitor GW6471. ConclusionP.cocos extract ameliorates hyperlipidemia and lipid accumulation by regulating cholesterol homeostasis in hepatocytes through PPARα pathway. This study provides evidence that supplementation with P.cocos extract could be a potential strategy for the treatment of hyperlipidemia.

Lipid metabolism-related gene expression in the immune microenvironment predicts prognostic outcomes in renal cell carcinoma.

Rates of renal cell carcinoma (RCC) occurrence and mortality are steadily rising. In an effort to address this issue, the present bioinformatics study was developed with the goal of identifying major lipid metabolism biomarkers and immune infiltration characteristics associated with RCC cases. The Cancer Genome Atlas (TCGA) and E-MTAB-1980 were used to obtain matched clinical and RNA expression data from patients diagnosed with RCC. A LASSO algorithm and multivariate Cox regression analyses were employed to design a prognostic risk model for these patients. The tumor immune microenvironment (TIME) in RCC patients was further interrogated through ESTIMATE, TIMER, and single-cell gene set enrichment analysis (ssGSEA) analyses. Gene Ontology (GO), KEGG, and GSEA enrichment approaches were further employed to gauge the mechanistic basis for the observed results. Differences in gene expression and associated functional changes were then validated through appropriate molecular biology assays. Through the approach detailed above, a risk model based on 8 genes associated with RCC patient overall survival and lipid metabolism was ultimately identified that was capable of aiding in the diagnosis of this cancer type. Poorer prognostic outcomes in the analyzed RCC patients were associated with higher immune scores, lower levels of tumor purity, greater immune cell infiltration, and higher relative immune status. In GO and KEGG enrichment analyses, genes that were differentially expressed between risk groups were primarily related to the immune response and substance metabolism. GSEA analyses additionally revealed that the most enriched factors in the high-risk group included the stable internal environment, peroxisomes, and fatty acid metabolism. Subsequent experimental validation in vitro and in vivo revealed that the most significantly differentially expressed gene identified herein, ALOX5, was capable of suppressing RCC tumor cell proliferation, invasivity, and migration. In summary, a risk model was successfully established that was significantly related to RCC patient prognosis and TIME composition, offering a robust foundation for the development of novel targeted therapeutic agents and individualized treatment regimens. In both immunoassays and functional analyses, dysregulated lipid metabolism was associated with aberrant immunological activity and the reprogramming of fatty acid metabolic activity, contributing to poorer outcomes.

Essential oil components of turmeric inhibit hepatic lipidification and liver fibrosis in a diet-induced NASH model rats

In this study, the fraction extracted from turmeric powder with 50% ethanol and fractionated with n-hexane were administered to diet-induced NASH model rats. NASH model was prepared with SD rats by feeding an originally designed choline-deficient, high-fat, high-fructose (HFF-CD) diet for 10 weeks. To the HFF-CD diet, hexane fraction and 50% ethanol fraction after hexane fractionation were added at 100 mg/kg body weight. 10 weeks later, blood samples and liver were collected for the following parameters: lipid weights, serum ALT, AST, TG, liver TG, TBARS levels, lipid metabolism-related gene expression and histopathological examination of the liver. As the results, the hexane fraction and 50% ethanol fraction showed a decrease in lipid weight, a decrease in hepatic TG, and activation of PPAR-α in the lipid metabolism-related gene test. These results suggest that the hexane fraction of turmeric has an inhibitory effect on fat accumulation in the liver by promoting lipid metabolism in NASH model rats.