Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased by polyunsaturated fatty acids BRYNN H. JONES, MARGARET A. MAHER, WILLIAM J. BANZ, MICHAEL B. ZEMEL, JAY WHELAN, PAMELA J. SMITH, AND NAIMA MOUSTAID Physiology Program and Department of Nutrition, University of Tennessee, Knoxville, Tennessee 37996-1900; and Department of Veterans Affairs Medical Center, East Orange, New Jersey 07019 Jones, Brynn H., Margaret A. Maher, William J. Banz, Michael B. Zemel, Jay Whelan, Pamela J. Smith, and Na’ima Moustai’d. Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased by polyunsatu- rated fatty acids. Am. J. Physiol. 271 (Endocrinol. Metab. 34): E44-E49, 1996.-Stearoyl-CoA desaturase (SCD) is a key regulatory enzyme in the synthesis of unsaturated fatty acids. Although regulation of hepatic SCD by obesity and polyunsaturated fatty acids (PUFA) has been well investi- gated, no studies have addressed whether similar regulation occurs in adipose tissue. We addressed these questions by feeding control (12% corn oil) and high-PUFA (48% corn oil) diets to lean and obese Zucker rats and analyzing SCD mRNA levels in adipose tissue and liver. We report that SCD mRNA content was dramatically elevated in adipose tissue of obese vs. lean rats on both diets and was significantly decreased by PUFA in both genotypes. Interestingly, we demonstrate that SCD expression was directly downregulated in a dose- dependent manner by PUFA in 3T3-Ll adipocytes. We con- clude that 1) obese Zucker rats overexpress the SCD gene in both liver and adipose tissue and 2) PUFA directly suppress SCD expression in adipocytes. Further studies will elucidate the mechanisms responsible for obesity- and PUFA-mediated regulation of SCD in adipose cells. 3T3-Ll adipocytes; Zucker rats; linoleate STEAROYL-COA DESATURASE (SCD) catalyzes the initial desaturation of long-chain fatty acids, primarily palmi- tate and stearate, at the Am9 position. The reaction catalyzed by SCD, which occurs predominantly in liver and adipose tissue, represents the first regulatory step in the formation of long-chain unsaturated fatty acids (8). Changes in the activity of SCD in tissues are reflected in cell membrane phospholipid composition. SCD therefore has the potential to regulate a variety of key physiological variables, such as insulin sensitivity (10) and metabolic rate (23), which have been shown to be influenced by the membrane fatty acid profile. Indeed, SCD activity has been shown to be elevated in the liver of various animal models of obesity, and a positive correlation between SCD activity in skeletal muscle and the percentage of body fat has recently been reported in human subjects (reviewed in Ref. 20). Although this repeated positive relationship between SCD and obesity provides no insight into the issue of cause or consequence, its prevalence across several obese models raises interesting questions regarding the physiological consequences of altered SCD expression. Regulation of SCD enzyme levels is exerted primarily through changes in the transcriptional rate of two SCD genes (SCD-1 and SCD-2), each of which encodes the same functional enzyme (26). Hepatic expression has been the model widely used to study regulation of SCD. Recent studies indicate that dietary fatty acids are a major factor in regulation of hepatic SCD levels. Ntambi (19) reported that dietary trilinolein (l&2) and triara- chidonin (20:4) decreased transcription of SCD-1 in mouse liver by up to 90% compared withthat in mice fed fat-free diets. This response was specific to polyun- saturated fatty acids (PUFA), because neither monoun- saturated nor saturated fatty acids exerted any effect on SCD gene transcription. Similar results have also been reported in vitro using isolated hepatocytes, sug- gesting a direct action of PUFA on SCD-1 gene expres- sion (13). Although the hepatic model has yielded interesting findings, it is not clear whether results obtained in this model can be extended to adipose tissue, which is also a predominant site of both SCD expression and lipid metabolism. In fact, few studies have addressed PUFA- mediated regulation of genes involved in lipid metabo- lism in adipose tissue. This is likely because previous studies that examined tissue specificity of lipogenic control by PUFA have yielded conflicting results. Clarke et al. (4), for example, reported that PUFA decreased lipogenesis in liver but not in adipose tissue and later concluded that PUFA effects on genes involved in lipid metabolism were liver specific (3). In contrast, Du and Kruger (7) and Demeyer et al. (5) reported suppression of both hepatic and adipose tissue lipogenesis by PUFA. Indirect evidence derived from tissue fatty acid compo- sition suggests that adipose tissue SCD activity is decreased by dietary PUFA (27), but no studies to date have directly investigated this possibility. Adipose tis- sue is a prominent site of both SCD expression and insulin action, and alterations in SCD expression may ultimately modulate insulin sensitivity. It is then impor- tant to investigate regulation of this enzyme in adipose tissue. It is also important to determine whether obesity- associated overexpression of SCD, previously noted in liver and skeletal muscle of several obese models, extends to adipose tissue. We examined these issues by analyzing adipose SCD-1 mRNA levels in lean and obese Zucker rats fed diets containing 12% (control) or 48% (high PUFA) of kilocalories as corn oil. These levels of PUFA were chosen on the basis of previous studies that examined the effects of dietary fat on lipid metabolism (27). We report here that hepatic and adipose SCD-1 mRNA levels are increased in obese vs. lean Zucker rats in both tissues examined. Interestingly, PUFA decreased E44 0193-1849/96 $5.00 Copyright o 1996 the American Physiological Society