Abstract
Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.
Highlights
The regulation of fatty acid–oxidation, fatty acid–synthesis and storage all play a vital role in the maintenance of normal intracellular lipid concentrations [1,2]
Anthropometric data and serum free fatty acids and leptin were, as expected, significantly greater in the morbidly obese patients, no significant differences were seen between the two groups of morbidly obese patients
The most relevant findings in this study are (a) the discrepancy between stearoyl-CoA desaturase 1 (SCD1) mRNA expression and SCD1 protein level in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT); (b) VAT and SAT SCD1 protein levels are clearly raised in morbidly obese patients; (c) VAT and SAT show different SCD1 mRNA expression and protein levels; (d) SCD1 mRNA expression levels are mainly associated with body mass index (BMI), sterol regulatory element binding protein-1 (SREBP-1) levels and the percentage of n-6 polyunsaturated fatty acids (PUFAs) in triglycerides; and (e) SCD1 protein levels vary according to insulin resistance and ATPase p97 levels
Summary
The regulation of fatty acid–oxidation, fatty acid–synthesis and storage all play a vital role in the maintenance of normal intracellular lipid concentrations [1,2]. Studies in mice have shown that stearoyl-CoA desaturase 1 (SCD1) may be a key piece in these processes [3]. SCD1 was proposed to play a vital role in the explanation of obesity in Mediterranean countries [4]. Experimental animal studies have revealed the association between SCD1 and obesity and insulin resistance [1,9]. Mice with a targeted disruption in the SCD1 gene are resistant to diet-induced weight gain and have increased insulin sensitivity compared with wild-type controls [7]. Loss of SCD1 activity is associated with greater insulin sensitivity in skeletal muscle [11]. A study in mice showed that SCD1 deficiency worsens the diabetes in obese mice [12]. Total SCD1 deficiency represents an extreme phenotype that may not be compared with human physiology
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