Alpha Omega Alpha Honor Medical Society

2011 Research Abstract

Estrogen and Retinoic Acid Interactions in the Regulation of Adipose Triglyceride Lipase

Investigator: Barbara Reichert, The Ohio State University College of Medicine, Columbus, Ohio

Mentors: Rudolf Zechner, Karl Franzens University, Graz, Austria, and Ouliana Ziouzenkova, Department of Human Nutrition, The Ohio State University, Columbus, Ohio

Visceral fat, seen in postmenopausal women, is a critical risk factor and predictor of mortality. Visceral obesity is a complex disorder involving dysregulation of fat storage and lipolysis. Identifying mechanisms and regulation of the rate-limiting enzyme of lipolysis in adipose tissue, adipose triglyceride lipase (ATGL), is key in understanding and treating this disorder, but the regulation of ATGL is currently unknown. Our previous studies implicated two vitamin A metabolites, retinaldehyde and retinoic acid (RA), as key regulators of female visceral fat accumulation. We now investigate the interaction between these metabolites and ATGL in adiposity.

Dietary vitamin A is converted to retinaldehyde and then irreversibly to RA by the aldehyde dehydrogenase 1 family of enzymes (Aldh1a1, a2, a3), primarily Aldh1a1. Female mice with genetic Aldh1a1 deficiency are protected from obesity via resistance to visceral fat accumulation when on a high fat diet and when deprived of estrogen by ovariectomy or age. Visceral adipose tissue from these mice shows increased ATGL protein compared to wild-type counterparts.

To elucidate if these in vivo effects were due to direct effects of vitamin A metabolites and/or estrogen on ATGL, we stimulated mature 3T3-L1 adipocytes and human SGBS adipocytes with retinaldehyde or RA in the presence and absence of estrogen. We measured ATGL protein by Western blot and activity by non-esterified fatty acid (NEFA)-release assay.

In 3T3-L1 adipocytes, retinaldehyde stimulated increased ATGL protein levels. Human SGBS adipocytes showed increased NEFA release after 3hr exposure to retinaldehyde (122% compared to control) or estrogen (112%), but did not show cumulative effects upon stimulation with both compounds together.

Our results suggest that retinaldehyde and estrogen separately stimulate lipolysis, potentially through a common pathway, and implicate ATGL as a mediator of this increased lipolysis.

Updated on July 9, 2012.

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