Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects

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.

Changes in SCD gene DNA methylation after bariatric surgery in morbidly obese patients are associated with free fatty acids

“…A recent study has shown that the treatment with palmitate for 48 h affects genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets31. As in a previous study of our group performed in adipose tissue, we have also found a negative association between mRNA expression in PBMC and FFA levels4. However, we have not found significant association between SCD mRNA expression and SCD methylation levels.…”

“…As in our previous study, serum SCD activity indices were not associated with SCD mRNA expression in PBMC, neither with SCD methylation levels4. This could be explained because this measurement of SCD activity in serum mainly reflect the hepatic activity of SCD, since these indices are derived from fatty acids present in VLDL, LDL and HDL, which have their origin mainly in the liver, not in PBMC33…”

“…SCD is an endoplasmic reticulum-bound enzyme that transform different saturated fatty acids into monounsaturated fatty acids (MUFA)2. Animal and human studies have revealed the association between SCD and obesity and insulin resistance34. Mice with a disruption in the SCD gene are resistant to diet induced weight gain and have increased insulin sensitivity when compared with wild-type controls5.…”

Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: Relationship with stearoyl-CoA desaturase activity

“…Moreover, it remains possible that Scd1 mRNA expression was up-regulated in adipose tissue (Mangravite et al, 2007), peripheral blood cells (Vik-Mo et al, 2008), and/or skeletal muscle (Hulver et al, 2005). Alternatively, atypical antipsychotic medications may up-regulate Scd1 protein expression and/or enzymatic activity independent of effects on Scd1 transcription, and elevations in SCD1 protein expression in the absence of corresponding elevations in SCD1 mRNA expression have been observed previously (Garcia-Serrano et al, 2010). …”

Fenretinide Induces Ubiquitin‐Dependent Proteasomal Degradation of Stearoyl‐CoA Desaturase in Human Retinal Pigment Epithelial Cells

“…Interestingly, deleting Scd1 expression has been shown to decrease ceramide synthesis by down-regulating SPT expression in mice skeletal muscle (Peter et al, 2009). Furthermore, Scd1 deficiency increased insulin sensitivity in mice, whereas increased SCD activity contributed to the insulin resistance in humans and animals (Dobrzyn et al, 2010; Garcia-Serrano et al, 2011; Gutierrez-Juarez et al, 2006; Peter et al, 2009; Rahman et al, 2003). Thus, it is possible that SCD could play an important role in mediating the effects of fenretinide on apoptosis and insulin signaling.…”