Inhibition of stearoyl CoA desaturase activity induces hypercholesterolemia in the cholesterol-fed hamster

Abstract

Reduction of stearoyl CoA desaturase (SCD) activity has been shown to induce resistance to diet-induced obesity in mice. In the present study, SCD was inhibited by feeding sterculic oil (SO) to male Golden Syrian Hamsters fed high-fat diets with or without added dietary cholesterol. In the absence of cholesterol, SO had little impact on adipose tissue mass or plasma lipoprotein concentrations. When cholesterol was included in the diet, inhibition of SCD resulted in reduced body weight, adipose tissue mass, and feed efficiency. These animals also exhibited a marked hypercholesterolemia, with an accumulation of free-cholesterolrich particles within the LDL density range, and reduced hepatic cholesterol esterification. This was accompanied by a 20-fold increase in plasma alanine aminotransferase, which was suggestive of significant hepatic damage. Hepatic acetyl CoA carboxylase and fatty acid synthase mRNA concentrations were reduced by feeding cholesterol and SO, whereas lipoprotein lipase and SCD mRNA were increased. These changes were associated with decreased hepatic sterol regulatory element binding protein 1a and 1c mRNA concentrations. Thus, inhibition of SCD activity in the cholesterol-fed hamster results in a reduction in overall body weight and adipose tissue deposition. However, this also causes marked hypercholesterolemia and potential liver

Sterculic Oil, a Natural SCD1 Inhibitor, Improves Glucose Tolerance in Obese ob/ob Mice

“…Overall, our data are consistent with previous reports demonstrating a robust inhibition of SCD1 activity with sterculic oil [9, 10, 59]. However, despite this reduction, the observed metabolic effects did not overlap completely with previous studies that have used alternative methods to ablate or attenuate SCD1.…”

“…A product that has yet to be thoroughly examined for its potential nutraceutical properties is sterculic oil (SO), a known natural inhibitor of stearoyl-CoA desaturase 1 (SCD1) [9, 10]. Sterculic oil contains two unique cyclopropenoic fatty acids, sterculic (55%), and malvalic (10%) acids [11, 12], which inhibit the enzymatic activity of SCD1 [9, 10]. Recently, SCD1, a major enzyme involved in fatty acid metabolism, has emerged as a potential pharmaceutical target for the treatment of obesity and type 2 diabetes [13, 14].…”

“…The health claims associated with these products should be based on scientific data demonstrating a biological effect (improved health or reduced disease risk) as well as a mechanism(s) of action. In vivo and in vitro studies have confirmed the ability of sterculic oil to attenuate SCD1 activity [9, 10, 19, 20]. Nonetheless, the metabolic consequences of SO consumption remain unclear.…”

De Novo Lipogenesis and Stearoyl-CoA Desaturase Are Coordinately Regulated in the Human Adipocyte and Protect against Palmitate-induced Cell Injury

“…Furthermore, SAFAs have also been shown to reduce insulin sensitivity (39), stressing the importance of desaturation of SAFAs in cell function. Although there are claims that SCD inhibition may provide a pharmaceutical means to combat obesity (40,41), this study and others provide evidence that SCD inhibition in the adipocyte may be detrimental to cell function and lead to unwanted side effects (42)(43)(44).…”

Fatty acid composition and some physicochemical characteristics of <em>Sterculia apetala</em> seed oils

“…Moreover, various biological activities have been observed after sterculic acid administration in cell cultures and animal models, showing beneficial as well as adverse results. Some studies have demonstrated that sterculic acid provokes reductions in body weight and adiposity, improvements in glucose tolerance and attenuates hepatic inflammation (Gomez et al, 2003;Major et al, 2008;Ortinau et al, 2012), while others have suggested adverse effects on smooth muscle proliferation, reproductive function and growth, induction of hypercholesterolemia and liver damage, and carcinogenic effects when given at high doses to rats (>1%) (Mujumdar et al, 2000;Major et al, 2008;Lee et al, 1971;Look et al, 2004;Pawlowski et al, 1985). Some of these effects have been related to the ability of sterculic acid to inhibit stearoyl-CoA desaturase activity (SCD, also known as Δ9 desaturase), a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), by the O 2 -dependent desaturation of palmitate (16:0) and stearate (18:0) (Gomez et al, 2003).…”