TITLE:
2,4-Dinitrophenol Downregulates Genes for Diabetes and Fatty Liver in Obese Mice
AUTHORS:
Qian Gao, Jiang He, Tao Liao, Qingping Zeng
KEYWORDS:
Obesity, Metabolic Disease, Low-Grade Inflammation, 2, 4-Dinitrophenol, Anti-Inflammation
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.3 No.9,
September
17,
2015
ABSTRACT: Whether obesity is a disease or a risk
factor of metabolic diseases including type 2 diabetes and fatty liver remains
debating, we report here that a high-fat diet (HFD) alone or HFD-combined
intramuscular injection with a high dose (1.2 mg/kg) of lipopolysaccharide
(LPS) induces mouse peripheral noninflammatory obesity. In contrast,
HFD-combined intraperitoneal injection with a low dose (0.25 mg/kg) of LPS
induces mouse visceral low-grade inflammatory obesity. While the
noninsulin-dependent diabetes mellitus (NIDDM) and nonalcoholic fatty liver
disease (NAFLD)- related genes are globally upregulated in HFD + low-dose LPS
mice, NIDDM and NAFLD genes are not extensively upregulated in HFD + high-dose
LPS mice. The mitochondrial uncoupler 2,4-dini- trophenol (DNP) in the dosage
of 16 mg/kg was found to exert a weight-reducing effect in obese mice by
compromising NF-κB-primed inflammatory responses, thereby down regulating NIDDM
and NAFLD genes. Conclusively, mouse visceral low-grade inflammatory obesity
that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.