Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD.

Previous experimental studies show that exposure to noise with high and audible frequencies causes multiple metabolic alterations, such as increased liver glycogen and triglycerides. However, the effect of exposure to sound with lower frequencies, such as high-intensity infrasound (frequency <20 Hz and sound pressure level >90 dB), on the liver lipid content is still unclear. As such, we aimed to study the effect of exposure to high-intensity infrasound of both normal and glucose intolerant rats on the liver lipid content. For this study, 79 wild-type male Wistar rats were randomly divided into two groups: G1, no treatment, and G2, induced glucose intolerance. Each of these two groups was randomly divided in two subgroups: s (animals kept in silence) and i (animals continuously exposed to high-intensity infrasound noise). At three noise-exposure time-points (1, 6 and 12 weeks) the rats were sacrificed, the liver was excised and hepatic lipids extracted. Data analysis was performed using a two-way ANOVA (p = 0.05). No significant effects due to interactions between the several factors exist on the liver lipid content (p=0.077). Moreover, no significant effects due to infrasound exposure (p=0.407) or glucose tolerance status (p=0.938) were observed. Our study shows that continuous exposure to high-intensity infrasound has no influence on the lipid content of the liver of both normal and glucose intolerant animals. This finding reinforces the need for further experimental studies on the physiological effects of infrasound due to its possible hazardous effects on human health.

Despite previous studies suggesting that choline and betaine ameliorate lipid accumulation in rat livers, the relative effectiveness of the two nutrients is unclear. We examined the efficacy of dietary supplementation with choline or betaine in ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in the rat liver. Male Wistar rats were fed control, B6-deficient, choline-supplemented B6-deficient, betaine-supplemented B6-deficient, or both choline and betaine-supplemented B6-deficient diets (all containing 9 g of l-methionine (Met)/kg) for 35 d. Two experiments were performed, i.e., one using 17 mmol/kg diet choline bitartrate, betaine anhydrous, and the combination and another using 8.5 mmol/kg diet. Rats fed a B6-deficient diet developed lipid accumulation in the liver with a reduction of plasma lipids induced by the disruption of Met metabolism. However, the addition of 17 mmol/kg diet choline or betaine was sufficient to ameliorate the disruptions of lipid and Met metabolism. Additionally, 8.5 mmol/kg diet choline ameliorated liver lipid deposition, while the same amount of betaine had no significant effects on liver or plasma lipid profiles. Supplementation with choline resulted in a higher liver betaine than that found using the same amount of betaine alone, although the overall liver betaine content was reduced in B6-deficient rats. Our findings indicate that choline is more effective than betaine in ameliorating B6 deficiency-related disruptions in Met metabolism and liver lipid accumulation by increasing liver betaine levels.

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model.

We investigated the efficacy of supplementing the diet with choline or betaine in ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in rat liver. Male Wistar rats were fed a control, B6-deficient, choline-supplemented (2, 4, or 6 g choline bitartrate/kg diet) B6-deficient diet or betaine-supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B6-deficient diet for 35 d; all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine supplementation attenuated liver lipid deposition and restored plasma lipid profiles to control levels. These treatments restored the disruptions in Met metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio induced by B6 deficiency in liver microsomes. These results suggest that choline and betaine ameliorated liver lipid accumulation induced by B6 deficiency via recovery of Met metabolism and very low-density lipoprotein secretion by restoring the supply of PC derived from PE.

OBJECTIVE: Persian leek is one of the most widely used herbal foods among Iranians. In this study, effects of oral administration of Persian leek on plasma and liver lipids were examined in hamster.
METHODS: Male Syrian hamsters were randomly divided into three groups: control (standard diet), high fat control (high-fat/high-cholesterol diet), Persian leek (high-fat/high-cholesterol diet + 1% per weight of diet from dried powdered Persian leek) for 14 weeks.
RESULTS: High fat diet increased plasma and liver lipids as compared to standard diet. Adding Persian leek to the high-fat/high-cholesterol diet resulted in no significant changes in the concentration of the plasma lipids or liver cholesterol. However, liver triglycerides (TG), plasma Alanine aminotransferase and gene expression of tumor necrosis factor- α were decreased in hamsters fed high-fat diet containing Persian leek as compared to high-fat diet only.
CONCLUSIONS: Persian leek might be considered as a herbal food that can reduce liver TG accumulation induced by high fat diets.

We evaluated the lactation performance, liver lipid content and plasma metabolites indicating the energy balance of dairy cows supplemented with conjugated linoleic acid (CLA) pre- and post-partum (PP) vs. only PP. A total of 60 cows were divided into three groups (n = 20). Daily diet of cows was supplemented with 14 g of CLA (7 g cis-9, trans-11 and 7 g trans-10, cis-12 isomers) from week 3 before the expected date of calving (group CLA1), or from the day of calving (group CLA2) until 77-91 days PP. Control cows were fed an isocaloric, isonitrogenous and isolipidic diet without CLA. Between week 3 and week 6 PP, the milk yield of cows in both CLA-treated groups was approximately 4.5 kg higher (p < 0.05) than in control. Milk fat concentrations decreased from week 3 and were lower in both CLA groups than in control (p < 0.01). Body condition score loss was lower (p < 0.05) in the CLA1 than in the control group on week 5 PP. By week 11 PP, the body condition of both CLA1 and CLA2 groups exceeded that of control. Plasma non-esterified fatty acid was lower in CLA1 compared to CLA2 and control during the early PP period (p < 0.05), while this difference faded away by the late PP period. Beta-hydroxybutyrate (BHBA) increased rapidly in all groups following calving. In CLA1 group, it began to decrease sooner than in CLA2 and control. The prevalence of subclinical ketosis (BHBA > 1.2 mm) was lower in CLA1 group than in CLA2 and control (p < 0.05). Liver biopsy analyses showed that CLA1 treatment decreased (p < 0.05) the total lipid content of liver compared to control at week 5 after calving. Our results show that CLA supplementation is more efficient in alleviating body mass mobilization and decreasing the incidence of subclinical ketosis when applied as early as 3 weeks before calving than started feeding after calving.

We investigated the efficacy of supplementing the diet with pteroylmonoglutamic acid (PGA), choline, or phosphatidylcholine (PC) in ameliorating the lipid accumulation in rat liver that is induced by vitamin B6 (B6) deficiency. In Experiment 1, male Wistar rats were fed a control, B6-deficient, or PGA-, choline-, or PC-supplemented (10 mg, 4 g, and 6.3 g/kg of diet, respectively) B6-deficient diet containing l-methionine at 9 g/kg of diet for 35 days. In Experiment 2, rats were fed a control, B6-deficient, or PC-supplemented (at 3.15, 6.3, or 12.6 g PC/kg of diet) B6-deficient diet for 35 days. Choline or PC supplementation ameliorated liver lipid deposition and returned plasma lipids to normal. Judging from these results, it appeared that B6 deficiency decreased the synthesis of PC in the liver, thereby decreasing the secretion of very low-density lipoproteins, and in consequence producing lipid accumulation in the liver and reductions of plasma lipids.

Tree nuts such as pecans (Carya illinoinensis) contain mostly oil but are also a source of polyphenols. Nut consumption has been linked to a reduction in serum lipid levels and oxidative stress. These effects have been attributed to the oil while overlooking the potential contribution of the polyphenols. Because the evidence regarding each fraction\'s bioactivity is scarce, we administered high-fat (HF) diets to male Wistar rats, supplementing them with pecan oil (HF+PO), pecan polyphenols (HF+PP) or whole pecans (HF+WP), and analysed the effects of each fraction. The HF diet increased the serum leptin and total cholesterol (TC) with respect to the control levels. The HF+WP diet prevented hyperleptinemia and decreased the TC compared with the control. The HF+WP diet upregulated the hepatic expression of apolipoprotein B and LDL receptor mRNAs with respect to the HF levels. The HF+PO diet reduced the level of triacylglycerols compared with the control. The HF+PP diet stimulated the hepatic expression of liver X receptor alpha mRNA. The HF+WP diet increased the activities of hepatic catalase, glutathione peroxidase and glutathione S transferase compared with the control, and decreased the degree of lipid peroxidation compared with the HF diet. The most bioactive diet was the WP diet.

OBJECTIVE: Sphingolipid de novo biosynthesis is related to nonalcoholic fatty liver disease or hepatic steatosis. However, the mechanism is still unclear. Sphingomyelin synthase (SMS), using ceramide as one of the substrates to produce sphingomyelin, sits at the crossroads of sphingolipid biosynthesis. SMS has 2 isoforms: SMS1 and SMS2. SMS2 is the major isoform in liver.
RESULTS: To investigate the relationship between liver SMS2 activity-mediated sphingolipid changes and hepatic steatosis, we used 2 mouse models: Sms2 liver-specific transgenic and Sms2 knockout mice. We found that Sms2 liver-specific transgenic livers have lower ceramide and higher sphingomyelin, whereas Sms2 knockout livers have higher ceramide and lower sphingomyelin. We also found that liver Sms2 overexpression promoted fatty acid uptake and liver steatosis, whereas Sms2 deficiency had an opposite effect in comparison with their respective controls. Importantly, the exogenous ceramide supplementation to Huh7 cells, a human hepatoma cell line, reduced the expression of peroxisome proliferator-activated receptor γ2 and its target genes, Cd36 and Fsp27. Peroxisome proliferator-activated receptor γ reporter analysis confirmed this phenomenon. Furthermore, peroxisome proliferator-activated receptor γ antagonist treatment significantly decreased triglyceride accumulation in Sms2 liver-specific transgenic liver.
CONCLUSIONS: We attributed these effects to ceramide that can suppress peroxisome proliferator-activated receptor γ2, thus reducing the expression of Cd36 and Fsp27 and reducing liver steatosis. After all, SMS2 inhibition in the liver could diminish liver steatosis.