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Nutrients 2014, 6(3), 950-973; doi:10.3390/nu6030950

Aldehyde Dehydrogenase 1A1: Friend or Foe to Female Metabolism?

Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
Author to whom correspondence should be addressed.
Received: 26 November 2013 / Revised: 8 February 2014 / Accepted: 18 February 2014 / Published: 3 March 2014
(This article belongs to the Special Issue Vitamin A and Carotenoids)
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In this review, we summarize recent advances in understanding vitamin A-dependent regulation of sex-specific differences in metabolic diseases, inflammation, and certain cancers. We focus on the characterization of the aldehyde dehydrogenase-1 family of enzymes (ALDH1A1, ALDH1A2, ALDH1A3) that catalyze conversion of retinaldehyde to retinoic acid. Additionally, we propose a “horizontal transfer of signaling” from estrogen to retinoids through the action of ALDH1A1. Although estrogen does not directly influence expression of Aldh1a1, it has the ability to suppress Aldh1a2 and Aldh1a3, thereby establishing a female-specific mechanism for retinoic acid generation in target tissues. ALDH1A1 regulates adipogenesis, abdominal fat formation, glucose tolerance, and suppression of thermogenesis in adipocytes; in B cells, ALDH1A1 plays a protective role by inducing oncogene suppressors Rara and Pparg. Considering the conflicting responses of Aldh1a1 in a multitude of physiological processes, only tissue-specific regulation of Aldh1a1 can result in therapeutic effects. We have shown through successful implantation of tissue-specific Aldh1a1−/− preadipocytes that thermogenesis can be induced in wild-type adipose tissues to resolve diet-induced visceral obesity in females. We will briefly discuss the emerging role of ALDH1A1 in multiple myeloma, the regulation of reproduction, and immune responses, and conclude by discussing the role of ALDH1A1 in future therapeutic applications.
Keywords: oestrogen; Raldh; alcohol dehydrogenase; lymphotactin; retinoids; tissue factor; PCOS; gender differences; Esr1; android obesity oestrogen; Raldh; alcohol dehydrogenase; lymphotactin; retinoids; tissue factor; PCOS; gender differences; Esr1; android obesity

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Petrosino, J.M.; DiSilvestro, D.; Ziouzenkova, O. Aldehyde Dehydrogenase 1A1: Friend or Foe to Female Metabolism? Nutrients 2014, 6, 950-973.

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