Lipid Metabolism In Obese Mice Research Articles

The structural characterization of a novel Chinese yam polysaccharide and its hypolipidemic activity in HFD-induced obese C57BL/6J mice

Obesity was considered as a rapidly growing chronic disease that influences human health worldwide. In this study, we investigated the primary structure characteristics of Chinese yam polysaccharide (CYP) and its role in regulating lipid metabolism in a high-fat diet (HFD)-fed obese mice. The molecular weight of CYP was determined to be 3.16 × 103 kDa. Periodic acid oxidation & smith degradation and nuclear magnetic resonance results suggested that CYP consists of 1 → 2, 1 → 2, 6, 1 → 4, 1 → 4, 6, 1→, or 1 → 6 glycoside bonds. The in vivo experiment results suggested that the biochemical indices, tissue sections, and protein regulation associated with lipid metabolism were changed after administering CYP in obese mice. In addition, the abundances of short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Lachnospiraceae_NK4A136_group, and Ruminococcaceae_UCG-014 were increased, and the abundances of bacteria Desulfovibrionaceae and Ruminococcus and metabolites of arginine, propionylcarnitine, and alloisoleucine were decreased after CYP intervention in obese mice. Spearman's correlation analysis of intestinal flora, metabolites, and lipid metabolism parameters showed that CYP may affect lipid metabolism in obese mice by regulating the intestinal environment. Therefore, CYP may be used as a promising nutritional intervention agent for lipid metabolism.

Isoleucine‐restricted diets improve high‐fat diet‐induced nonalcoholic fatty liver disease via regulating insulin resistance and gut microbiota

AbstractObesity, caused by a long‐term high‐fat diet, is a risk factor for insulin resistance and nonalcoholic fatty liver disease (NAFLD). The gut microbiota plays an important role in NAFLD development by producing lipopolysaccharides (LPS). Isoleucine (ILE), as one of the branched‐chain amino acids (BCAAs), has a negative effect on glucose and lipid metabolism in obese mice. Therefore, we speculated that isoleucine‐restricted diets could prevent high‐fat diet‐induced insulin resistance and NAFLD. For this purpose, 30 C57BL/6J mice received a control check diet (CK), a high‐fat diet (HFD), and a isoleucine‐restricted diet (IR) for 12 weeks, respectively. The current study revealed that IR diets reversed HFD‐induced weight gain, increased fasting glucose levels, and lipid metabolism disorder. Furthermore, IR diets attenuated HFD‐induced hepatic inflammation by regulating the LPS/TLR4/NF‐κB signaling pathway. Moreover, hepatic insulin resistance and gluconeogenesis disorder were significantly improved by IR diets. In addition, IR diets reshaped HFD‐induced gut microbiota imbalance, reflected in decreasing the proportion of Proteobacteria phylum and LPS contents. Taken together, our studies support that restricting isoleucine in high‐fat diets was a novel means of preventing obesity‐induced NAFLD and insulin resistance.

Di-2-ethylhexyl phthalate disrupts hepatic lipid metabolism in obese mice by activating the LXR/SREBP-1c and PPAR-α signaling pathways

Di-2-ethylhexyl phthalate (DEHP), a widely utilized plasticizer, has been described as a potential obesogen based on in vivo disruption of hepatic lipid homeostasis and in vitro promotion of lipid accumulation. However, limited literature exists regarding the specific ramifications of DEHP exposure on obese individuals, and the precise mechanisms underlying the adverse effects of DEHP exposure remain unclear. This study aimed to assess the impact of DEHP on hepatic lipid metabolism in obese mice by comparing them to normal mice. Following a 10-week DEHP exposure period, the obese mice exhibited higher blood lipid levels, more severe hepatic steatosis, and more infiltrations of inflammatory cells in liver tissue than normal mice. Interestingly, the body weight of the mice exhibited no significant alteration. In addition, transcriptomic analyses revealed that both lipogenesis and fatty acid oxidation contributed to hepatic lipid metabolism dysregulation following DEHP exposure. More specifically, alterations in the transcription of genes associated with hepatic lipid metabolism were linked to the different responses to DEHP exposure observed in normal and obese mice. Additionally, the outcomes of in vitro experiments validated the in vivo findings and demonstrated that DEHP exposure could modify hepatic lipid metabolism in normal mice by activating the LXR/SREBP-1c signaling pathway to promote lipogenesis. At the same time, DEHP exposure led to inhibition of the Camkkβ/AMPK pathway to suppress β-fatty acid oxidation. Conversely, in obese mice, DEHP exposure was found to be associated with the stimulation of both lipogenesis and fatty acid oxidation via activation of the LXR/SREBP-1c and PPAR-α signaling pathways, respectively. The findings presented in this study first elucidate the contrasting mechanisms underlying DEHP-induced liver damage in obese and normal mice, thereby offering valuable insights into the pathogenesis of DEHP-induced liver damage in individuals with obesity.

Effect of globin peptide on female fertility in aging granulosa cell-specific Nrg1 knockout mice.

Ovarian fibrosis contributes to age-related ovarian dysfunction. In our previous study, we observed ovarian fibrosis in both obese and aging mice with intracellular lipid droplets in the fibrotic ovaries. Although the importance of mitochondria in ovarian fibrosis has been recognized in pharmacological studies, their role in lipid metabolism remains unclear. Globin peptide (GP), derived from hemoglobin, enhances lipid metabolism in obese mice. This study aimed to elucidate the importance of lipid metabolism in ovarian fibrosis by using GP. Treatment of ovarian stromal cells with GP increased mitochondrial oxygen consumption during β-oxidation. Lipid accumulation was also observed in the ovaries of granulosa cell-specific Nrg1 knockout mice (gcNrg1KO), and the administration of GP to gcNrg1KO mice for two months reduced ovarian lipid accumulation and fibrosis in addition to restoring the estrous cycle. GP holds promise for mitigating lipid-related ovarian issues and provides a novel approach to safeguarding ovarian health by regulating fibrosis via lipid pathways.

[Mechanism of Xianglian Pills in improving dyslipidemia in obese mice induced by high-fat diet based on network pharmacology and intestinal flora].

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.

Combined exposure to deoxynivalenol facilitates lipid metabolism disorder in high-fat-diet-induced obesity mice

Deoxynivalenol (DON) is a trichothecene toxin that mainly produced by strains of Fusarium spp. DON contamination is widely distributed and is a global food safety threat. Existing studies have expounded its harmful effects on growth inhibition, endocrine disruption, immune function impairment, and reproductive toxicity. In energy metabolism, DON suppresses appetite, reduces body weight, triggers lipid oxidation, and negatively affects cholesterol and fatty acid homeostasis. In this study, high-fat diet (HFD) induced obese C57BL/6J mice were orally treated with 0.1 mg/kg bw/d and 1.0 mg/kg bw/d DON for 4 weeks. The lipid metabolism of mice and the molecular mechanisms were explored. The data showed that although DON reduced body weight and fat mass in HFD mice, it significantly increased their serum triglyceride concentrations, disturbance of serum lipid metabolites, impaired glucose, and resulted in insulin intolerance in mice. In addition, the transcriptional and expression changes of lipid metabolism genes in the liver and epididymis (EP) adipose indicate that the DON-mediated increase in serum triglycerides is caused by lipoprotein lipase (LPL) inhibition in EP adipose. Furthermore, DON down-regulates the expression of LPL through the PPARγ signaling pathway in EP adipose. These results are further confirmed by the serum lipidomics analysis. In conclusion, DON acts on the PPARγ pathway of white adipose to inhibit the expression of LPL, mediate the increase of serum triglyceride in obese mice, disturb the homeostasis of lipid metabolism, and increase the risk of cardiovascular disease. This study reveals the interference mechanism of DON on lipid metabolism in obese mice and provides a theoretical basis for its toxic effect in obese individuals.

Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice

Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin. Unfortunately, metformin does not protect against antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be salsalate, the prodrug of salicylate, which acts synergistically with metformin to improve indices of glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of salsalate, metformin and a combination of both drugs, on weight gain and indices of metabolic health in female mice treated with the antipsychotic, olanzapine. Herein we demonstrate that salsalate was equally as effective as metformin in protecting against olanzapine induced weight gain and liver lipid accumulation with no additional benefit of combining both drugs. Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications.

Effects of Mealworm Fermentation Extract and Soy Protein Mix Ratio on Hepatic Glucose and Lipid Metabolism in Obese-Induced Mice.

Previous studies found that mealworm fermentation extract (TMP) reduced alcoholic hepatic steatogenesis. This study examined how the ratio of TMP and soy protein (SP) mix affected glucose and lipid metabolism in obese mice given a high-fat diet (HFD). Mice were given HFD supplemented with 100% SP or the following three ratios of TMP and SP mix for 12 weeks: 20% (S4T1), 40% (S3T2), and 60% (S2T3) TMP. When compared to the SP group, the S2T3 group had considerably lower body weight gain and food consumption. When compared to the SP group, the S2T3 group had slightly lower blood insulin and leptin levels, as well as a lower homeostasis model assessment of insulin resistance score. The use of TMP instead of SP reduced the size of epididymal adipose tissue cells. An increase in the extent of substitution of SP with TMP inhibited the gene expression of hepatic fructolysis/gluconeogenesis (KHK, ALDOB, DLD, and FBP1), lipogenesis (FAS, SCD1, CD36, and DGAT2), and its transcriptional factors (PPARγ and ChREBP). Furthermore, the S2T3 group dramatically reduced the expression of hepatic genes implicated in endoplasmic reticulum stress (PDI) and antioxidant defense (SOD1). The 60% TMP mix, in particular, reduced the expression of hepatic glucose and lipid metabolismrelated genes in HFD-fed mice. The manufacturing of functional processed goods may be accomplished by combining SP and TMP in a 2:3 ratio.

Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.

Combination of Pioglitazone and Metformin Actions on Liver Lipid Metabolism in Obese Mice.

Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.

Nuciferine ameliorates high‐fat diet‐induced disorders of glucose and lipid metabolism in obese mice based on the gut–liver axis

AbstractHigh‐fat diets (HFDs) can trigger lipid accumulation, insulin resistance, and inflammatory responses in the body, causing glucose and lipid metabolism dysfunction. This study aimed to explore the role of nuciferine on HFD‐induced disorders of glucose and lipid metabolism in obesity mice models, and further to identify the possible underlying mechanisms. In our experiments, nuciferine effectively ameliorated HFD‐induced insulin resistance by IRS/PI3K/AKT pathway, and alleviated HFD‐induced lipid accumulation via AMPK‐mediated regulation of FAS and ATGL expression. Nuciferine also suppressed HFD‐induced intestinal pathological damage, as evidenced by the improvement of intestinal barrier integrity and the increasing in expressions of tight junction proteins of claudin, ZO‐1, and occludin. In addition, 16S rRNA gene sequencing of the fecal microbiota suggested that nuciferine changed the diversity and the composition of gut microbiota in HFD‐fed mice. Nuciferine decreased the ratio of Firmicutes/Bacteroidetes, the relative abundance of LPS‐producing genus Desulfovibrio and the bacteria which involved in lipid metabolism. In summary, nuciferine ameliorated the disorders of glucose and lipid metabolism in obese mice via balancing the gut–liver axis.

The Effect of Guisangyou Tea on Abnormal Lipid Metabolism in Mice Induced by High-Fat Diet.

This study was aimed to investigate the effect of Guisangyou tea (GSY tea) in improving abnormal lipid metabolism in mice with obesity induced by a high-fat diet (HFD). The results showed that intervention of the water extract of GSY tea (WE) decreased serum levels of lipids, and positively regulated the related antioxidant enzyme activities and the inflammatory factors in the serum and liver. In the liver, the mRNA and protein expression levels of sterol regulatory element-binding proteins-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD-1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) related to lipid synthesis were downregulated, and the mRNA and protein expression levels of the farnesoid X receptor (FXR) and small heterodimer partner (SHP) related to bile acid production were upregulated. The results demonstrate that GSY tea can improve abnormal lipid metabolism in obese mice by improving the body's antioxidant capacity, regulating the inflammatory state, and reducing the synthesis of lipids and increasing the production of bile acids. GSY tea can be processed and utilized as a safe and effective resource for improving abnormal lipid metabolism.

FAM3A maintains metabolic homeostasis by interacting with F1-ATP synthase to regulate the activity and assembly of ATP synthase

Reduced mitochondrial ATP synthase (ATPS) capacity plays crucial roles in the pathogenesis of metabolic disorders. However, there is currently no effective strategy for synchronously stimulating the expressions of ATPS key subunits to restore its assembly. This study determined the roles of mitochondrial protein FAM3A in regulating the activity and assembly of ATPS in hepatocytes. FAM3A is localized in mitochondrial matrix, where it interacts with F1-ATPS to initially activate ATP synthesis and release, and released ATP further activates P2 receptor-Akt-CREB pathway to induce FOXD3 expression. FOXD3 synchronously stimulates the transcriptions of ATPS key subunits and assembly genes to increase its assembly and capacity, augmenting ATP synthesis and inhibiting ROS production. FAM3A, FOXD3 and ATPS expressions were reduced in livers of diabetic mice and NAFLD patients. FOXD3 expression, ATPS capacity and ATP content were reduced in various tissues of FAM3A-deficient mice with dysregulated glucose and lipid metabolism. Hepatic FOXD3 activation increased ATPS assembly to ameliorate dysregulated glucose and lipid metabolism in obese mice. Hepatic FOXD3 inhibition or knockout reduced ATPS capacity to aggravate HFD-induced hyperglycemia and steatosis. In conclusion, FAM3A is an active ATPS component, and regulates its activity and assembly by activating FOXD3. Activating FAM3A-FOXD3 axis represents a viable strategy for restoring ATPS assembly to treat metabolic disorders.

Improving obesity and lipid metabolism using conjugated linoleic acid

Conjugated linoleic acid (CLA) can prevent fatty acid accumulation induced by a high-fructose diet and improve lipid metabolism disorders in patients. We aimed to investigate the effect of CLA on obesity and lipid metabolism and its possible mechanism. Eight-month-old male BKS.Cg-Dock7m +/+ Leprdb /JNju (db/db) mice (n=12) were fed a CLA mix composed of equivalent c9, t11-CLA and t10, c12-CLA for 1 month. The effect of CLA on body weight, water and food intake, and triglyceride (TG) and total cholesterol (TC) levels was investigated. PPARα, PPARγ and CD36 expression was determined by quantitative PCR and western blotting. Additionally, the expression of these three genes was studied in HepG2 cells treated with CLA and linoleic acid. CLA treatment notably reduced the dietary and water intake of db/db mice, effectively reduced body weight, and decreased serum TG and TC levels (p<0.05). Increased expression of PPARα (p<0.05) and decreased expression of CD36 (p<0.001) were observed in the liver of mice that were fed CLA. CLA increased PPARα expression (p<0.001) and decreased PPARγ (p<0.001) and CD36 expression (p<0.01) in HepG2 cells. Our results showed that CLA can improve lipid metabolism in obese mice through upregulation of PPARα expression and downregulation of CD36 expression.

Saponins from Panax japonicus alleviate adipose tissue fibrosis and metabolic dysfunction in high-fat-diet-induced obese mice

Introduction: Adipose tissue fibrosis is a typical feature of adipose tissue dysfunction in obese individuals, which is closely related to metabolic diseases. Objective: To explore the effect and mechanism of Saponins from Panax japonicus (SPJ) on adipose tissue fibrosis in obese mice induced by high fat diet (HFD). Materials and methods: We established a HFD induced obese mice model. Then the obese mice were treated with 90 mg/kg SPJ by oral gavage for 10 weeks. The levels of adipose tissue fibrosis and molecules related to signaling pathways were measured. Then the effects of SPJ on TGFβ1- induced fibrosis in 3T3-L1 differentiated adipocytes were evaluated. Results: SPJ reduced body weight, fat accumulation, and improved glucose and lipid metabolism in obese mice. SPJ decreased collagen deposition and expressions of fibrotic genes in epididymal white adipose tissue (eWAT) of obese mice. SPJ decreased the levels of TGFβ1 protein and pSmad2, and increased the expression of PPARγ and PGC1α, thus alleviating oxidative stress in eWAT. Consistently, SPJ inhibited TGFβ1- induced fibrosis in 3T3-L1 differentiated adipocytes. Conclusions: SPJ may alleviate adipose tissue fibrosis and improve obesity by inhibiting TGFβ1/Smad2 and activating PPARγ/PGC1α pathway. SPJ is expected to become an efficient medicine for treatment of obesity.

Concurrent betaine administration enhances exercise-induced improvements to glucose handling in obese mice

Background and aimsBetaine supplementation has been shown to enhance hepatic lipid metabolism in obese mice and improve exercise performance in healthy populations. We examined effects of betaine supplementation, alone or in combination with treadmill exercise, on the metabolic consequences of high fat diet (HFD)-induced obesity in mice. Methods and resultsMale C57BL/6 J mice were fed chow or HFD. After 15 weeks, HFD mice were split into: HFD, HFD with betaine (1.5% w/v), HFD with treadmill exercise, and HFD with both betaine and exercise (15 m/min for 45min, 6 days/week; n = 12/group) for 10 weeks. Compared to HFD mice, body weight was significantly reduced in exercise and exercise-betaine mice, but not in mice given betaine alone. Similarly, adiposity was reduced by exercise but not by betaine alone. HFD-induced glucose intolerance was slightly improved by exercise, but not with betaine alone.Significantly greater benefits were observed in exercise-betaine mice, compared to exercise alone, such that GTT-outcomes were similar to controls. This was associated with reduced insulin levels during ipGTT, suggesting enhanced insulin sensitivity. Modest benefits were observed in fatty acid metabolism genes in skeletal muscle, whilst limited effects were observed in the liver. HFD-induced increases in hepatic Mpc1 (mitochondrial pyruvate carrier 1) were normalized by all treatments, suggesting potential links to altered glucose metabolism. ConclusionsOur data show that drinking 1.5% betaine was sufficient to augment metabolic benefits of exercise in obese mice. These processes appear to be facilitated by altered glucose metabolism, with limited effects on hepatic lipid metabolism.

Astragaloside IV ameliorates metabolic disorder in db/db obese mice as a PPARγ antagonist

Metabolic disorder is highly related to obesity, insulin resistance, hypertension, and hyperlipidemia. The present study found that astragaloside IV (ASI) attenuated metabolic disorder related symptoms and modulated hepatic lipid metabolism associated gene mRNA expression in db/db mice. ASI inhibited rosiglitazone-induced adipocyte differentiation of 3T3-L1 cells, and lipid accumulation in palmitic acid (PA)-induced HepG2 cells with down-regulated mRNA expression of lipogenesis-related genes. In addition, it was predicted to bind to the ligand binding domain (LBD) of PPARγ and inhibit its transactivity. Collectively, our study suggested that ASI improves lipid metabolism in obese mice probably through suppressing PPARγ activity.

Aerobic exercise improves adipogenesis in diet-induced obese mice via the lncSRA/p38/JNK/PPARγ pathway

Adipogenesis is one of the triggers of obesity, which is a risk factor for various metabolic diseases. Long noncoding RNA steroid receptor RNA activator (lncRNA-SRA) is closely related to adipogenesis and p38/JNK mitogen-activated protein kinase mediates lipid production by regulating peroxisome proliferator-activated receptor gamma (PPARγ). Aerobic exercise can be efficient in improving adiposity and losing weight. Hence, we hypothesize that aerobic exercise ameliorates obesity by affecting the SRA/p38/JNK/PPARγ pathway and downstream target genes. The broad approaches used to test hypotheses are as follows. Spectrophotometer detected C57BL/6J mice blood lipid level; hematoxylin and eosin-stained fat tissue to check the grade of epididymis fat; quantitative polymerase chain reaction and Western blot detected messenger RNA expression and protein levels. Injected lncRNA-SRA virus vector to overexpress SRA. After 8 weeks of aerobic exercise intervention, obese mice showed significant improvements in body weight, white fat weight, lipid levels, and the Lee index. Aerobic exercise significantly inhibited the expression of SRA, activated the p38/JNK signaling pathway, further inhibited the expression of PPARγ and downstream target genes, and improved obesity. Aerobic exercise intervention improved lipid metabolism in obese mice, and the mechanism may be related to the regulation of the LncSRA/p38/JNK/PPARγ signaling pathway.

Effects of Buffalo Milk and Cow Milk on Lipid Metabolism in Obese Mice Induced by High Fat.

The aim of this study was to evaluate the effects of buffalo milk and cow milk on lipid metabolism in obese mice. Milk composition analysis showed fat, protein, and total solid content in buffalo milk was higher than cow milk, while the lactose content of buffalo milk was lower than cow milk. After milk metabolite extraction and LC-MS/MS analysis, differential metabolites were mainly enriched in “linoleic acid metabolism pathways,” “pentose and glucuronate interconversion pathways,” and “metabolism of xenobiotics by cytochrome P450 pathways.” We fed three groups of C57BL/6J mice (n = 6 per group) for 5 weeks: (1) high-fat diet group (HFD group); (2) high-fat diet + buffalo milk group (HBM group); and (3) high-fat diet + cow milk group (HCM group). Our results showed that body weight of mice was significantly decreased in HBM and HCM groups from 1 to 4 weeks compared with the HFD group. The mRNA expression of ACAA2, ACACB, and SLC27A5 genes involved in the lipid metabolism in liver tissue were significantly elevated in HCM group, relatively to HFD and HBM group. In addition, the adipocyte number, size and lipid accumulation in the liver were significantly decreased in HCM group compared with the HFD group by H&E staining and oil red O staining, but was not change in HBM group. The mRNA levels of TNF-α and IL-1β inflammatory genes were significantly increased in HBM group, relatively to HFD and HCM group, which is consistent with results from inflammatory cell infiltration and tissue disruption by colon tissue sections. In conclusion, dietary supplementation of cow milk has beneficial effects on loss of weight and lipid metabolism in obese mice.

Leukemia inhibitory factor protects against liver steatosis in nonalcoholic fatty liver disease patients and obese mice

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. However, the molecular mechanisms that promote dysregulation of hepatic triglyceride metabolism and lead to NAFLD are poorly understood, and effective treatments are limited. Leukemia inhibitory factor (LIF) is a member of the interleukin-6 cytokine family and has been shown to regulate a variety of physiological processes, although its role in hepatic triglyceride metabolism remains unknown. In the present study, we measured circulating LIF levels by ELISA in 214 patients with biopsy-diagnosed NAFLD as well as 314 normal control patients. We further investigated the potential role and mechanism of LIF on hepatic lipid metabolism in obese mice. We found that circulating LIF levels correlated with the severity of liver steatosis. Patients with ballooning, fibrosis, lobular inflammation, and abnormally elevated liver injury markers alanine transaminase and aspartate aminotransferase also had higher levels of serum LIF than control patients. Furthermore, animal studies showed that white adipose tissue–derived LIF could ameliorate liver steatosis through activation of hepatic LIF receptor signaling pathways. Together, our results suggested that targeting LIF-LIF receptor signaling might be a promising strategy for treating NAFLD.