Genipin alleviates high‐fat diet‐induced hyperlipidemia and hepatic lipid accumulation in mice via miR‐142a‐5p/SREBP‐1c axis

Abstract

Hyperlipidemia is a chronic disorder which plays an important role in the development of cardiovascular diseases, type 2 diabetes, atherosclerosis, hypertension, and nonalcoholic fatty liver disease. Genipin (GNP) is a metabolite from genipioside, which is an active component of the traditional Chinese medicine Gardenia jasminoides Ellis, and has been recognized as a beneficial compound against metabolic disorders. However, whether it can correct overnutrition-induced dyslipidemia is still unknown. In this study, the effects of GNP on attenuating hyperlipidemia and hepatic lipid accumulation were investigated using normal and obese mice induced with a high-fat diet (HFD) and primary hepatocytes treated with free fatty acids. We also sought to identify potential targets of GNP to mediate its effects in the liver. We found that obese mice treated with GNP showed a decrease in the body weight, serum lipid levels, as well as hepatic lipid accumulation. Besides, GNP regulated hepatic expression levels of lipid metabolic genes, which are important in maintaining systemic lipid homeostasis. At the molecular level, GNP increased the expression levels of miR-142a-5p, which bound to 3' untranslated region of Srebp-1c, an important regulator of lipogenesis, which thus led to the inhibition of lipogenesis. Collectively, our data demonstrated that GNP effectively antagonized HFD-induced hyperlipidemia and hepatic lipid accumulation in mice. Such effects were achieved by regulating miR-142a-5p/SREBP-1c axis.

Genipin Reverses HFD-Induced Liver Damage and Inhibits UCP2-Mediated Pyroptosis in Mice

“…Takeuchi et al [44] found that GNP improved acute liver dysfunction by suppressing TNF-α production. In our previous study, we also found that GNP alleviated hepatic lipid accumulation via the miR-142a/SREBP-1c axis [45]. Collectively, these data show that GNP has therapeutic benefits in patients with liver disease.…”

A novel berberine‐metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats

“…Several transcription factors, such as C/EBP‐α and PPAR‐Ɣ are particularly important in the regulation of adipogenesis . SREBP‐1 c is a key regulatory protein that modulates ectopic lipid deposition, which is highly transcribed during hepatic steatosis . In the present study, BMH473 can regulate the protein expression levels of C/EBP‐α, PPAR‐Ɣ and SREBP‐1 c, as well as the mRNA expression levels of lipid metabolism genes, including LDLR , ADIPOQ , FAS , Scd 1 and PBEF1 .…”

“…31,32 SREBP-1 c is a key regulatory protein that modulates ectopic lipid deposition, which is highly transcribed during hepatic steatosis. [33][34][35] In the present study, BMH473 can regulate the protein expression [36][37][38] Several studies have demonstrated the elevated levels of pro-inflammatory cytokines (TNF-α, IL-1 β and IL-6) in obesity and T2DM. 2,39-43 NF-κB is a transcription factor that plays an essential role in immune and inflammatory responses via regulating inflammatory cytokine expression.…”

Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics

“…The expression level of C-C chemokine receptor type 5 (CCR5) and chemokine receptor type 4 (CXCR4) on CD4+ Tcellswere decreased in cells treated with this iridoid glycoside, demonstrated that this iridoid glycoside restricts HIV-1 replication on the early stage of HIV infection [35] Antiproliferative activities Deacetyl asperuloside 806.4 µg/mL K562 chronic myelogenous leukemic cells Significantly increased caspase 3 activity (p < 0.05) [16] AChE inhibitory Lupulinoside 134.0 µM GST, AChE Lupulinoside exhibited different levels of GST, AChE inhibitory [41] Anti-obesity Genipin 20 mg/kg High-fat diet-fed obese mice Regulating miR-142a-5p/SREBP-1c axis, led to the inhibition of lipogenesis [96] Anti-osteoporosis activity Aucubin 1, 2.5, 5 µM MG63 cells Improved osteoblast differentiation and enhanced the levels of BMP2 (bone morphogenetic proteins-2) in MG63 cells [97] Nuezhenelenoliciside -MC3T3-E1 cells Increased the proliferation of pre-osteoblast MC3T3-E1 cells, possessed anti-osteoporosis activity [11]…”

“…In addition, the highest concentrations of picroside I and III were found in kidneys, while picroside II was found in the liver. Moreover, it was found that picroside II exhibits the slowest metabolism with the terminal elimination half-lives (T1/2) were reported to be 0.941 ± 0.235 h [96]. Another study showed that because picroside I, II has a lipophilic and ionizable state, it can be completely metabolized [128].…”