Galgeun-tang modulates lipid, glucose, and energy metabolism in diet-induced obesity across cellular, nematode, and murine models

TL;DR

Galgeun-tang, a traditional Korean herbal formula, shows anti-obesity effects by improving glucose and lipid metabolism in multiple models, suggesting it could be a multi-targeted treatment for obesity and metabolic disorders.

Contribution

This study demonstrates Galgeun-tang's multi-targeted metabolic benefits across cellular, nematode, and mouse models, offering preclinical support for its use in obesity.

Findings

Galgeun-tang improved glucose uptake and insulin signaling in muscle cells.

In mice, it reduced body weight gain, improved glucose tolerance, and decreased liver fat.

In nematodes, it reduced lipid accumulation, prolonged lifespan, and modulated insulin signaling genes.

Abstract

Galgeun-tang (GGT) is a traditional Korean multi-component formulation composed of several botanical drugs and has long been prescribed for febrile and musculoskeletal disorders. With the global rise in obesity and obesity-related metabolic diseases, there is increasing demand for safer and multi-targeted therapeutic strategies. However, the systemic metabolic effects and anti-obesity potential of GGT remain incompletely understood.

The anti-obesity effects of GGT were evaluated using a tiered experimental approach comprising C2C12 myotubes, high-fat diet (HFD)-induced obese C57BL/6J mice, and Caenorhabditis elegans (C. elegans) exposed to high-glucose conditions. In vitro analyses assessed glucose uptake, gene expression, and protein signaling pathways. In mice, body weight, glucose tolerance, serum biochemical parameters, histological changes, and hepatic and adipose gene expression were examined. In C. elegans, lifespan, lipid and glucose accumulation, and insulin signaling–related gene expression were analyzed following treatment with GGT or metformin (MET).

GGT enhanced glucose uptake and increased the expression of insulin-responsive and mitochondrial regulatory genes in C2C12 myotubes. In HFD-fed mice, GGT attenuated body weight gain, improved glucose tolerance and insulin sensitivity, and alleviated hepatic steatosis and adipose hypertrophy, accompanied by suppression of lipogenic genes and induction of β-oxidation markers. In C. elegans, GGT reduced lipid and glucose accumulation, prolonged lifespan, and modulated the expression of insulin signaling–related genes, including daf-16 and daf-2. Across models, GGT exerted metabolic benefits in a dose- and context-dependent manner, with effects comparable to those of MET.

GGT improves obesity-related metabolic dysfunction by coordinately regulating glucose homeostasis, lipid metabolism, and energy expenditure across cellular, nematode, and murine models. These findings provide preclinical evidence supporting GGT as a multi-targeted herbal intervention for obesity and metabolic disorders and warrant further targeted mechanistic studies and clinical investigations.

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