Fat production in adipocytes is strongly stimulated by insulin. By controlling the activity of the pyruvate dehydrogenase and the acetyl-coA enzymes, insulin promotes unsaturated fatty acid synthesis. It also promotes glucose uptake and induces SREFB1, which activates the transcription of genes that stimulate lipogenesis.
Clinical studies have repeatedly shown that even though insulin resistance is usually associated with obesity, the membrane phospholipids of the adipocytes of obese patients generally still show an increased degree of fatty acid unsaturation.This seems to point to an adaptive mechanism that allows the adipocyte to maintain its functionality, despite the increased storage demands associated with obesity and insulin resistance.
A study conducted in 2013 found that, while INSIG1 and SREBF1 mRNA expression was decreased in the adipose tissue of obese mice and humans, the amount of active SREBF1 was increased in comparison with normal mice and non-obese patients. This down regulation of INSIG1 expression combined with the increase of mature SREBF1 was also correlated with the maintenance of SREBF1-target gene expression. Hence, it appears that, by down regulating INSIG1, there is a resetting of the INSIG1/SREBF1 loop, allowing for the maintenance of active SREBF1 levels. This seems to help compensate for the anti-lipogenic effects of insulin resistance and thus preserve adipocyte fat storage abilities and availability of appropriate levels of fatty acid unsaturation in face of the nutritional pressures of obesity.
