CU06-1004 modulates the adenosine monophosphate (AMP)-associated protein kinase (AMPK) signaling pathway and inhibits lipogenesis in 3T3-L1 adipocytes and high-fat diet-induced obese mice.

Abstract

AIMS:

The endothelial dysfunction blocker CU06-1004 exhibits anti-inflammatory effects in chronic diseases. Obesity is a major cause of chronic inflammation, and the effect of CU06-1004 on obesity has not been studied yet. Therefore, in this study, we investigated the anti-obesity properties of CU06-1004 in 3T3-L1 adipocytes and high-fat diet-induced obese mice.

METHODS:

Differentiated 3T3-L1 adipocytes were treated with various concentrations of CU06-1004 (0-20 μg/mL) and subjected to Oil Red O staining to determine the levels of lipid droplet and intracellular triglyceride accumulation. Additionally, high-fat diet-induced obese C57BL/6J mice were administered with a low (10 mg/kg/day) or high (20 mg/kg/day) oral dose of CU06-1004. Finally, the expressions of genes and proteins involved in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway were assessed by real-time polymerase chain reaction and Western blot, respectively.

KEY FINDINGS:

The CU06-1004 administration reduced lipid accumulation in the 3T3-L1 adipocytes by inhibiting the expressions of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, fatty acid binding protein 4, and fatty acid synthase in a dose-dependent manner. Additionally, it significantly increased the phosphorylation of AMPKα and acetyl-CoA carboxylase in the 3T3-L1 adipocytes. An oral administration of high dose of CU06-1004 in the obese mice significantly decreased their body weight and the mesenteric white adipose tissue weight. Furthermore, CU06-1004 improved hepatic steatosis by reducing lipogenesis, besides improving insulin resistance and exerting systemic anti-inflammatory effects.

SIGNIFICANCE:

CU06-1004 may have therapeutic potential in the prevention of obesity and obesity-related disorders.

• Authors: Cho-Rong Bae, Young-Guen Kwon
• Journal: Life sciences (Life Sci) Vol. 296 Pg. 120440 (May 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35240161 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• CU06-1004
• Saponins
• AMP-Activated Protein Kinases

Topics

• 3T3-L1 Cells
• AMP-Activated Protein Kinases (metabolism)
• Adipocytes (metabolism)
• Adipose Tissue, White (drug effects, metabolism)
• Animals
• Body Weight (drug effects, physiology)
• Cell Differentiation (drug effects)
• Diet, High-Fat (adverse effects)
• Glucose Tolerance Test
• Lipid Metabolism (drug effects)
• Lipogenesis (drug effects, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Saponins (pharmacology)
• Signal Transduction (drug effects)