Triglyceride Accumulation In Rats Research Articles

Androgens exacerbate hepatic triglyceride accumulation in rats with polycystic ovary syndrome by downregulating MTTP expression.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is closely associated with insulin resistance, glucose and lipid metabolism disorders. Patients with PCOS have a significantly higher risk of non-alcoholic fatty liver disease and are associated with hyperandrogenemia (HA). However, the exact mechanism by which HA exacerbates hepatic steatosis in PCOS has not yet been fully elucidated. This work aims to investigate the effects and underlying mechanisms of androgens on hepatic triglyceride (TG) metabolism in rats with PCOS. Twenty-four female Sprague-Dawley rats were randomly divided into four groups (6 rats/group): control, high-fat diet (HFD), PCOS, and PCOS + flutamide (Flu). Changes in the estrous cycle, liver and ovarian tissue sections, serum total testosterone, serum and liver biochemical indicators, and key enzymes involved in TG metabolism were studied. Hepatocyte steatosis and TG accumulation were more evident in the PCOS group than in the control and HFD groups. The PCOS group showed apparent increases in the levels of serum alanine aminotransferase, aspartate aminotransferase, TG, free fatty acid, fasting insulin, and homeostasis model assessment of insulin resistance. Hepatic VLDL and apoB-100 levels decreased in the PCOS group. After Flu was administered to block the actions of androgens, the above abnormalities had been improved. The expression of MTTP was greatly decreased in the PCOS group and significantly increased after Flu administration. Hepatic steatosis in PCOS rats was correlated with HA. Androgens may exacerbate hepatic TG accumulation by downregulating MTTP expression in PCOS.

A combined extract containing Schisandra chinensis (SCE) reduced hepatic triglyceride accumulation in rats fed a high-sucrose diet.

The online version contains supplementary material available at 10.1007/s10068-023-01464-1.

Marginal iron deficiency enhances liver triglyceride accumulation in rats fed a high-sucrose diet

We investigated whether marginal iron-deficiency (MID) without anemia influences liver lipid accumulation in rats. Ingestion of a MID diet in which the iron concentration was half of AIN-93 formulation (iron-adequate, IA) for 3weeks decreased liver iron concentration without anemia. We then evaluated the influence of the MID diet on liver lipid accumulation in combination with a high-sucrose (HS) diet and confirmed that the HS-MID diet successfully decreased liver iron concentration without anemia. Additionally, a significant increase in liver triglyceride concentration was found, accompanied by upregulation of hepatic fatty acid synthase expression in the rats fed the HS-MID diet compared to those in the rats fed an HS-IA diet, although no difference was observed in plasma transaminase activity and hepatic interleukin-1β expression. These results suggest that MID enhances de novo lipid synthesis via upregulation of lipogenic gene expression in combination with sucrose in the diet. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; HS, high sucrose; IA, iron adequate; ID, iron deficiency; MID, marginal irondeficiency; NAFLD, non-alcoholic fatty liver disease.

Prolonged fasting elicits increased hepatic triglyceride accumulation in rats born to dexamethasone-treated mothers

We investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX. These modulations were accompanied by accumulation of hepatic triglycerides (TG). Sixty-hour fasted DEX also showed increased citrate synthase (CS) activity, ATP citrate lyase (ACLY) content, and pyruvate kinase 2 (pkm2), glucose transporter 1 (slc2a1) and lactate dehydrogenase-a (ldha) expressions. Hepatic AKT2 was increased in 60-hour fasted DEX, in parallel with reduced miRNAs targeting the AKT2 gene. Altogether, we show that metabolic programming by prenatal dexamethasone is characterized by an unexpected hepatic TG accumulation during prolonged fasting. The underlying mechanism may depend on increased hepatic glycolytic flux due to increased pkm2 expression and consequent conversion of pyruvate to non-esterified fatty acid synthesis due to increased CS activity and ACLY levels. Upregulation of AKT2 due to reduced miRNAs may serve as a permanent mechanism leading to increased pkm2 expression.

Rice bran water extract attenuates pancreatic abnormalities in high-fat diet-induced obese rats

Purpose: To investigate the protective potential of rice bran water extract (RBE) from Khao Dawk Mali 105 on pancreatic abnormalities in high-fat diet (HFD)-induced obese rats.Methods: Male Sprague-Dawley rats were divided into 4 groups: control group, HFD group, and HFD group treated with RBE at 2,205 or 4,410 mg/kg/day. After 4 weeks, body weight, glucose homeostatic parameters, and pancreatic fat accumulation were assessed. mRNA expression levels of sterol regulatory element-binding protein-1c (SREBP-1c), insulin receptor substrate-2 (IRS-2), glucose transporter-2 (GLUT-2) and glucokinase (GK) genes in pancreas were also analyzed.Results: Compared with HFD group, two doses of RBE-treated rats significantly (p < 0.05) reversed HFD-induced obesity, hyperglycemia, impaired glucose tolerance and pancreatic triglyceride accumulation in rats. Histological examination of HFD-induced obese rats revealed fat droplets in acinar cells, but these alterations were ameliorated in RBE-treated rats. RBE treatment showed significantly (p < 0.05) decreased SREBP-1c expression, and also significantly (p < 0.05) increased IRS-2, GLUT-2 and GK expressions in pancreas.Conclusion: RBE consumption may attenuate pancreatic abnormalities by inhibiting fat accumulation, as well as enhancing insulin sensitivity and glucose sensing in the pancreas of HFD-induced obese rats.Keywords: Rice bran, Obesity, Pancreatic steatosis, Insulin signaling, Glucose sensor

Blackcurrant Suppresses Metabolic Syndrome Induced by High-Fructose Diet in Rats.

Increased fructose ingestion has been linked to obesity, hyperglycemia, dyslipidemia, and hypertension associated with metabolic syndrome. Blackcurrant (Ribes nigrum; BC) is a horticultural crop in Europe. To induce metabolic syndrome, Sprague-Dawley rats were fed 60% high-fructose diet. Treatment with BC (100 or 300 mg/kg/day for 8 weeks) significantly suppressed increased liver weight, epididymal fat weight, C-reactive protein (CRP), total bilirubin, leptin, and insulin in rats with induced metabolic syndrome. BC markedly prevented increased adipocyte size and hepatic triglyceride accumulation in rats with induced metabolic syndrome. BC suppressed oral glucose tolerance and protein expression of insulin receptor substrate-1 (IRS-1) and phosphorylated AMP-activated protein kinase (p-AMPK) in muscle. BC significantly suppressed plasma total cholesterol, triglyceride, and LDL content. BC suppressed endothelial dysfunction by inducing downregulation of endothelin-1 and adhesion molecules in the aorta. Vascular relaxation of thoracic aortic rings by sodium nitroprusside and acetylcholine was improved by BC. The present study provides evidence of the potential protective effect of BC against metabolic syndrome by demonstrating improvements in dyslipidemia, hypertension, insulin resistance, and obesity in vivo.

Effect of the peroxisome proliferator LY171883 on triglyceride accumulation in rats fed a fat-free diet

LY171883 is a leukotriene D 4 antagonist that induces peroxisome proliferation in the rodent liver. Like many peroxisome-proliferating agents, it causes transient lipid accumulation and several other changes in hepatic lipid metabolism. The effect of LY171883 on lipid metabolism was studied further in rats maintained on a fat-free diet. Administration of a fat-free diet for 14 days caused a 5.6-fold increase in liver triglycerides associated with a 3.3-fold increase in fatty acid synthetase. Co-administration of 0.1% LY171883 increased liver triglycerides slightly, whereas 0.3% LY171883 prevented the accumulation of triglycerides. Furthermore, treatment with 0.3% LY171883 reversed the fatty liver in rats pretreated with the fat-free diet for 14 days. Fatty acid synthetase activity increased comparably in all treatment groups, indicating that 0.3% LY171883 did not prevent the lipogenic response to a fat-free diet. In rats treated with 0.3% LY171883, peroxisomal β-oxidation increased 9.5-fold, mitochondrial β-oxidation 4.8-fold, carnitine palmitoyltransferase I 1.9-fold, and plasma ketones 3-fold. In the 0.1% dose group the increases in these parameters were smaller. The data indicate that 0.3% LY171883 sufficiently increased mitochondrial and peroxisomal β-oxidation such that fatty acids generated by lipogenesis were preferentially oxidized rather than esterified to triglycerides. In the 0.1% dose group oxidation was only mildly increased, and the excess fatty acids continued to be esterified.

A study of the relationships between carbon tetrachloride-induced lipid peroxidation and liver damage in rats pretreated with vitamin E

The relationships between the peroxidation of musomal lipids and the early liver damage have been investigated in rats pretreated with progressively higher doses of α-tocopherol (vit. E) and intoxicated with various amounts of carbon tetrachloride. Pretreatment of rats with vit. E at 25 mg 100g body wt. has minor effects on both the peroxidation of musomal lipids and the liver triglyceride accumulation in rats poisoned with CC1 4 at 250 μl 100g body wt. However, a decrease of the peroxidative reaction and of the liver steatosis occurs when the rats are pretreated with progressively higher doses of vit.E. A close correlation exists between the two phenomena, when the intoxication is accomplished with CC1 4 at 250 μ1 100 g body wt. Also, the musomal concentration of α-tocopherol is strictly correlated to both the decrease of musomal lipoperoxidation and the decrease of liver triglyceride accumulation. The CCl 4-induced impairment of musomal glucose-6-phosphatase and the incorporation of 14C from 14CC1 4 into liver musomal lipids are not affected by vit. E pretreatment. The extent of musomal lipoperoxidation is not correlated to the liver triglyceride accumulation when vit. E-pretreated rats are given CC1 4 at 25 or 2.5 μ1 100 g body wt. However, a correlation between lipoperoxidation and liver steatosis occurs when non-pretreated rats are challenged with the three different doses of the halogenated hydrocarbon.