DNP Downregulates Genes For Diabetes and Fatty Liver in Mice

[jaa]

https://peerj.com/preprints/1229.pdf

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.

It looks like LPS doesn't matter much intramuscularly, but has some pretty bad consequences in low doses when injected into the gut. DNP can help with that.