Leptin gene transfer into muscle increases lipolysis and oxygen consumption in white fat tissue in ob/ob mice

The effects of leptin production in ob/ob mice injected with a plasmid expression vector containing mouse leptin cDNA in the tibialis anterior muscle were investigated. A significant reduction in food intake (-18%, p<0.01) along the experimental period was found after DNA injection, while differences in body weight gain were only significant (-41%, p<0.05) when determined between days 2-9 of the study. Concerning adipocytes metabolism, there was a significant increase in oxygen consumption in vitro (+34%, p<0.05) and in basal lipolysis (+151%, p<0.05) in DNA-injected mice compared to PBS-injected animals. Our results confirm that functional leptin can be produced in muscle and released into the blood stream and give new support to the fact that leptin may have direct auto- or paracrine effects on adipocytes, possibly contributing to the weight- and fat-reducing effects of leptin in ob/ob mice. (C) 1998 Academic Press.