Gracilaria chorda subcritical water ameliorates hepatic lipid accumulation and regulates glucose homeostasis in a hepatic steatosis cell model and obese C57BL/6J mice

ETHNOPHARMACOLOGICAL RELEVANCERed seaweed, known as Rhodophyta, has a long history of use in traditional Asian medicine, including Traditional Chinese Medicine and Ayurveda. It is believed to have cooling and detoxification properties. Red seaweed species, such as Gracilaria, have been used in traditional remedies to address various conditions, such as inflammation, thyroid disorders, and digestive issues.AIM OF THE STUDYObesity is a risk factor of hepatic steatosis, a hallmark of non-alcoholic fatty liver disease (NAFLD) that affects nearly 25% of the worldwide population. Gracilaria chorda (GC) contains bioactive peptides that may be applicable in the prevention of metabolic syndrome diseases. This study investigated the effects of GC subcritical water extract at 210 °C (GCSW210) on preventing liver injury and lipid and glucose dysregulation in an oleic acid (OA)-induced hepatic steatosis cell model (HepG2) and high-fat diet (HFD)-induced obese animal model (C57BL/6J mice).MATERIALS AND METHODSHuman hepatoma HepG2 cells were exposed to 0.1 mM OA for 24 h to induce hepatic steatosis and C57BL/6J mice were fed a HFD for 13 weeks. For lipid accumulation, triglyceride (TG) content was measured in both models, along with free fatty acid (FFA), plasma glucose, and insulin levels in HFD-fed mice. Protein expression of master regulators of adipogenesis and lipogenesis, as well as cholesterol and mitochondrial biosynthesis, was studied via western blotting in hepatic steatosis-induced in vitro and in vivo models. In addition, protein expression of the insulin signaling cascade in skeletal muscle tissues of HFD-fed mice was studied.RESULTSGCSW210 significantly decreased lipid accumulation in HepG2 cells exposed to OA and suppressed the expression of lipogenic factors, such as sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase. In addition, GCSW210 abrogated transcription factors related to cholesterol biosynthesis, such as SREBP-2 and low-density lipoprotein receptor. Similarly, FFA, TG, serum glutamic acid, aspartate transaminase, alanine transferase, plasma glucose, and insulin levels were also significantly reduced in GCSW210-treated HFD-fed mice, which were comparable to the positive control mice treated with Garcinia cambogia extract. Additionally, GCSW210 enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase in the hepatic tissues of HFD-fed mice. Moreover, GCSW210 treatment improved insulin