NEW YORK (Reuters Health) - Adenovirus-induced hyperleptinemia transforms white adipocytes into “fat-burning cells” rich in mitochondria, researchers report in the Proceedings of the National Academy of Sciences, published online February 9. This finding may lead to new therapeutic strategies for obesity, senior author Dr. Roger H. Unger and colleagues suggest.
When fat is lost as a result of dietary restriction or insulin deficiency, adipocytes secrete fatty acids, which are oxidized to ketones in the liver. When hyperleptinemia is induced by adenovirus-mediated transfer of the leptin gene, however, there is neither ketonemia nor an increase in plasma free fatty acid levels, the researchers note.
To examine the changes associated with leptin-transformed white adipocytes, Dr. Unger, of the University of Texas Southwestern Medical Center in Dallas, and his team administered adenovirus containing rat leptin cDNA into diabetic fatty rats.
The animals dropped from an average of 280 grams to 207 grams in 14 days and their food intake was reduced by 30%. Plasma leptin levels rose from 3.5 ng/mL to 265 ng/mL on day 7, falling again to 36 ng/mL at day 14. The sectional area of adipocytes in the epididymal fat pad decreased from about 4000 µm² to an average 102 µm².
The gene expression profile, say the investigators, “revealed striking up-regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (an up-regulator of mitochondrial biogenesis not normally expressed in white fat), increased uncoupling proteins-1 and -2, and down-regulation of lipogenic enzymes.”
The fat loss differed from that induced by dietary restriction, in that it was lost more rapidly and was not accompanied by ketonemia or loss of lean body mass. The fat loss persisted for months.
The team points out that in rats with diet-induced obesity, leptin levels in the interstitial fluid surrounding the adipocytes are increased. They hypothesize that “to maintain their vital function of fuel storage and conservation, the adipocytes must mount a powerful defense against their own leptin to prevent wasteful loss of their fat stores, such as we induced here.”
They conclude that pharmacologic inactivation of normally released leptin may be a way to induce intracellular fatty acid oxidation that would “make obesity impossible."<
Source: Proc Natl Acad Sci USA 2004. [ Google search on this article ]
MeSH Headings:Biological Therapy: Cell Line: Cell Line, Transformed: Cells, Cultured: Genetic Engineering: Genetic Techniques: Investigative Techniques: Therapeutics: Gene Therapy: Leptin: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
