👤 Yuki Shuto

Multi-organ regulation underlies metabolic health, especially in the context of adipose-liver dysfunction during obesity. Previous findings identified Melinjo seed extract (MSE) as a promising modulator of metabolic disorders, although its active component remained unknown. Gnetin C, a trans-resveratrol dimer from MSE, likely serves as the key factor, yet its direct metabolic role remains unclear. Here, Gnetin C was administered to high-fat diet (HFD)-fed mice, which significantly improved body weight and fasting glucose, attributed to enhanced adiponectin (APN) multimerization. In adipose tissue, Gnetin C directly promotes APN multimerization and suppresses fat accumulation by up-regulating the PPARγ-DsbA-L axis, while concurrently modulating hepatic Sirt1, which may contribute to increased FGF21 production. This paracrine FGF21 signaling, suggested by elevated Fgfr1 in hepatocytes and βKlotho in adipocytes, further augments APN multimerization. These findings underscore the importance of a multi-tissue approach to obesity management and position Gnetin C as an integrative therapeutic candidate, restoring metabolic balance via dual adipose and hepatic effects in HFD mice. Show less

The impact of Graves' hyperthyroidism treatment on lipid metabolism remains unclear. This prospective observational study aimed to clarify the changes in lipid profiles and associated metabolic pathways, including cholesterol synthesis, absorption, and low-density lipoprotein (LDL) receptor regulation, following treatment. Seventeen patients newly diagnosed with Graves' hyperthyroidism were enrolled and followed for 6 months after achieving euthyroid status. Serum lipids (total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides), apolipoproteins, non-cholesterol sterols (markers of cholesterol synthesis and absorption), proprotein convertase subtilisin/kexin type 9 (PCSK9), and lipoprotein lipase (LPL) levels were measured at baseline, at euthyroid status (Eu-0M), and 6 months after euthyroid status (Eu-6M). After treatment, serum total cholesterol, LDL-C, and HDL-C levels increased rapidly compared to baseline, while triglyceride levels showed a delayed but significant increase at Eu-6M. Levels of apolipoprotein (apo) AI, AII, B, and CIII increased significantly after treatment, whereas apo B-48 increased only at Eu-6M, and apo CII and apo E remained unchanged. Markers of cholesterol synthesis (lathosterol) and absorption (sitosterol, campesterol, and cholestanol) increased significantly after treatment, indicating enhanced cholesterol metabolism. Circulating PCSK9 levels increased significantly and remained elevated, while LPL levels did not change significantly. Treatment of Graves' hyperthyroidism rapidly increases cholesterol levels through enhanced cholesterol synthesis and absorption, possibly mediated by increased circulating PCSK9. Show less