2,4-Dinitrophenol Downregulates Genes for Diabetes and Fatty Liver in Obese Mice

Whether obesity is a disease or a risk factor of chronic diseases including diabetes and fatty liver remains debating. We report here that a high-fat diet (HFD) alone or HFD and intramuscular injection of mice with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces the peripheral noninflammatory obesity. In contrast, HFD and intraperitoneal injection of mice with a low dose (0.25 mg/kg) of LPS induces the 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-dinitrophenol (DNP) was found to exert a weight-reducing effect in obese mice by downregulating NF-κB-primed inflammatory response accompanying with NIDDM and NAFLD genes, thereby abrogating inflammatory hepatic injury. In conclusion, visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.