Hexane-Isopropanolic Extract of Tungrymbai, a North-East Indian fermented soybean food prevents hepatic steatosis via regulating AMPK-mediated SREBP/FAS/ACC/HMGCR and PPARα/CPT1A/UCP2 pathways

Abstract

This study for the first time examined the prophylactic role of Tungrymbai, a well-known fermented soybean food of North-East India, against hepatic steatosis. Treatment with hexane-isopropanolic (2:1, HIET) but not hydro-alcoholic (70% ethanol, HAET) extract dose-dependently (0.1, 0.2, or 0.3 µg/mL) reduced the intracellular lipid accumulation as shown by lower triglyceride levels and both Oil Red O and Nile Red staining in palmitate (PA, 0.75 mM)-treated hepatocytes. Immunobloting, mRNA expression, and knock-down studies demonstrated the role of AMPK-mediated SREBP/FAS/ACC/HMGCR and PPARα/CPT1A/UCP2 signaling pathways in facilitating the beneficial role of HIET against lipid accumulation in PA-treated hepatocytes. Animal studies further showed a positive effect of HIET (20 µg/kg BW, 8 weeks, daily) in regulating AMPK/SREBP/PPARα signaling pathways and reducing body weight gain, plasma lipid levels, and hepatic steatosis in high fat diet (HFD)-fed mice. Histological analyses also revealed the beneficial effect of HIET in reducing hepatic fat accumulation in HFD mice. Chemical profiling (HRMS, IR, and HPLC) demonstrated the presence of menaquinone-7 (vitamin K2) as one of the bio-active principle(s) in HIET. Combining all, this study demonstrates the positive effect of HIET on reducing hepatic steatosis via regulating AMPK/SREBP/PPARα signaling pathway.

Dietary Bile Acids Enhance Growth, and Alleviate Hepatic Fibrosis Induced by a High Starch Diet via AKT/FOXO1 and cAMP/AMPK/SREBP1 Pathway in Micropterus salmoides

“…There is no prior evidence about the regulation relationship of the phosphorylation status of AMPK with MLD in fish, but previous studies found that fatty acid treatment or lipid-enriched diet inhibited AMPK phosphorylation and AMPK activation suppressed lipogenesis in rainbow trout (Polakof et al, 2011; Libran-Perez et al, 2015; Velasco et al, 2018). SREBP1 is a key transcription factor regulating lipogenesis and ACC and FASN are its downstream genes (Dihingia et al, 2018). It was well documented that hepatic lipid accumulation was closely related to the induction of SREBP1 expression (Pai et al, 2013) and AMPK/SREBP pathway had critical functions in the development of MLD (Kohjima et al, 2008; Jung et al, 2011; Li et al, 2011).…”

“…It was well documented that hepatic lipid accumulation was closely related to the induction of SREBP1 expression (Pai et al, 2013) and AMPK/SREBP pathway had critical functions in the development of MLD (Kohjima et al, 2008; Jung et al, 2011; Li et al, 2011). AMPK phosphorylation attenuated hepatic steatosis and fatty liver disease, etc., by inhibiting the expression of SREBP1, and further the inhibition of ACC and FASN (Li et al, 2011; Lee et al, 2015; Dihingia et al, 2018). The increased cAMP, up-regulated P-AMPK protein and depressed mRNA level of SREBP1, ACC, and FASN demonstrated that cAMP/AMPK/SREBP1 was an important pathway to decrease hepatic lipid accumulation by dietary BA.…”

“…It was reported that cAMP (cyclic adenosine monophosphate)/AMPK/SREBP (sterol regulatory element-binding protein) pathway plays a very important regulatory role in metabolic diseases (fatty liver, obesity, diabetes, etc.) (Lee et al, 2014, 2015; Li et al, 2018), in which, AMPK/SREBP pathway was widely studied and recognized to play a key role in the development of MLD related to energy metabolism disorder (Li et al, 2011; Lee et al, 2015; Dihingia et al, 2018). Until now, there were no reports of BA functions on nutrient metabolism and related disease by regulating the AKT and AMPK pathway in fish.…”

Atorvastatin promotes AMPK signaling to protect against high fat diet‑induced non‑alcoholic fatty liver in golden hamsters

“…Collectively, the present results indicate that AMPK is one of the main targets of Ato involved in the preventive effects of Ato on NAFLD. Numerous previous studies have indicated that PPARα is downstream of AMPK and Akt, and that its expression level is regulated by Akt (27)(28)(29). Therefore, the mRNA and protein expression levels of PPARα and PPARGC1A were investigated in the liver tissues of the hamsters in the present study.…”

Medium- and long-chain triglyceride propofol reduces the activity of acetyl-coenzyme A carboxylase in hepatic lipid metabolism in HepG2 and Huh7 cells

“…The energy sensor AMP-activated protein kinase (AMPK) is a key player in the regulation of energy metabolism [14151617] through its repression of fatty acid and TG synthesis [18]. Importantly, AMPK regulates hepatic lipid metabolism via the phosphorylation of its well-recognized downstream target ACC [19202122].…”