Berberine improves glucogenesis and lipid metabolism in nonalcoholic fatty liver disease

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is considered a critical hepatic manifestation of metabolic syndrome. Berberine (BBR) exerts anti-hyperglycemic and anti-dyslipidemic effects and can also ameliorate NAFLD. Thus, BBR might exert its therapeutic effect on NAFLD by improving glucolipid metabolism. Here, we investigated the aspects and extent to which glucolipid metabolism were affected by BBR in rats with NAFLD.MethodsThree groups of Sprague–Dawley rats were studied: a control group (n = 6) fed a normal chow diet and a NAFLD group (n = 6) and a NAFLD + BBR group (n = 6) fed a high-fat diet. Normal saline and BBR (150 mg/kg body weight/day for 16 weeks) were administered by gavage. All rats were infused with isotope tracers. The rates of glucose appearance (Raglu), gluconeogenesis (GNG) and glycerol appearance (Ragly) were assessed with 2H and 13C tracers, whereas the rates of hepatic lipogenesis and fatty acid β oxidation were measured using the 3H tracer.ResultsWhen the NAFLD model was successfully induced by administering a high-fat diet, body weight, insulin resistance and dyslipidemia were significantly increased. After the BBR treatment, weight loss, decreased lipid profiles and HOMA-IR, and increased ISI were observed. Meanwhile, BBR reduced Raglu, GNG and hepatic lipogenesis, whereas the rate of fatty acid β oxidation in skeletal muscle showed an increasing trend. Ragly showed a decreasing trend. Based on the results of the histological analysis, BBR obviously attenuated the ectopic liver fat accumulation.ConclusionsBBR improved NAFLD by inhibiting glucogenesis and comprehensively regulating lipid metabolism, and its effect on inhibiting hepatic lipogenesis was much stronger. The improvement may be partly mediated by weight loss. Berberine might be a good choice for patients with NAFLD and glucose metabolic disorder. Future clinical trials need to be conducted to confirm these effects.

Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitis via the ROS/TXNIP Axis

“…Several studies have explored the therapeutic effects of BBR on NASH in murine models (Qiang et al, 2016;He Q. et al, 2017;Zhao et al, 2017;Feng et al, 2018;Luo et al, 2019) and humans (Chang et al, 2016;Wei et al, 2016); Qiang et al demonstrated that demethyleneberberine attenuated lipid accumulation and inflammatory factors secretion with activation of AMPK and inhibition of oxidative stress in MCD diet feeding mice and db/db mice (Qiang et al, 2016). Feng et al compared the effects of BBR, curcumin, and lovastatin on NAFLD rats and found that BBR in combination with curcumin exhibited better ameliorative effects on rats with non-alcohol fatty liver than lovastatin (Feng et al, 2018).…”

The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution

“…Ten male Wistar rats and thirty male GK rats (3 weeks old) were bred and housed locally under a 12/12-h light/darkness cycle in a temperature-controlled room (22 ± 2°C) with free access to food and water. After 1 week of acclimation, the animals were all given a high-fat diet (HFD: 40% carbohydrate, 20% protein and 40% fat) (Zhao et al 2017) for 8 weeks. Then, the animals were randomly divided into four groups and given the high-fat diet continuously for 12 weeks.…”

“…Fasting insulin (FINS) levels were also assayed at the 0th, 4th and 12th weeks using an ELISA kit (Shibayaji, Japan). Then, the homeostatic model assessment index (HOMA-IR) and the insulin sensitivity index (ISI) were calculated from the fasting blood glucose (FBG) and FINS levels using the following formulas: HOMA-IR = FBG × FINS/22.5 and ISI = ln(1/(FBG × FINS)) (Zhao et al 2017). After 12 weeks of treatment, leptin and adiponectin levels were also assayed with ELISA kits (Crystal, USA).…”

“…In addition, 3 H 2 O generated from the process of [9,10-3 H]-palmitic acid β-oxidation was obtained by removing the lipids with chloroform. Next, 3 H radioactivity from both TG and 3 H 2 O was determined using liquid scintillation counting (LS6500 Multipurpose Scintillation Counter, Beckman) as previously described (Zhao et al 2017).…”

Chondroitin Sulfate Elicits Systemic Pathogenesis In Mice By Interfering With Gut Microbiota Homeostasis

“…Additionally, BER is under investigation to determine whether it may have applications as a drug in treating diabetes, hyperlipidemia, and cancer. Recently, BER has been proven to improve glucogenesis and lipid metabolism in NAFLD (Zhao et al, 2017), perhaps mainly acting on the visceral organs in addition to the gut microbiota per se.…”