Type 2 diabetes (T2D), the most common form of diabetes (90%), is strongly associated to obesity. Approximately 90% of people diagnosed with T2D are either overweight or obese. The strong association of T2D to obesity – “diabesity” - has emphasized the role of adipose tissue and lipids in the development of the disease. The two hallmarks of type 2 diabetes are insufficient insulin secretion and insulin resistance, i.e. decreased insulin sensitivity in target tissues of insulin. The mechanisms underlying these defects are incompletely understood, but ectopic fat accumulation in for instance the liver, visceral adipose tissue and insulin-producing beta-cells and low-grade inflammation appear central in the pathogenesis. Ectopic fat accumulation may be a result of insufficient expansion of subcutaneous adipose tissue in response to nutrient overload. The overall aim of our research is to elucidate mechanisms underlying the development insulin resistance and insulin secretion defects in T2D with a focus on adipose tissue and lipid metabolism. Knowledge about these mechanisms will lead to novel concepts for the prevention and treatment of obesity and T2D. To achieve our goals, we employ a broad approach, ranging from structure-function studies of proteins, to cellular studies, to studies of animal models of obesity and diabetes to clinical intervention studies. Examples of specific aims that we are currently addressing include: 1) Role of hormone-sensitive lipase, mostly known as a key enzyme in fatty acid mobilization, as a determinant in adipogenesis and energy expenditure; 2) Role of adiponutrin in normal physiology and in the development of liver steatosis; 3) impact of vitamin D insufficiency, and accompanying secondary hyperparathyroidism, on the development of insulin resistance and T2D and 4) exploration of antidiabetic and cardioprotective effects of berries.
- Ström, K., Gundersen, T.E., Hansson, O., Lucas, S., Fernandez, C., Blomhoff, R. and Holm, C. (2009) Hormone-sensitive lipase (HSL) is also a retinyl ester hydrolase:evidence from mice lacking HSL. FASEB J. 23:2307.
- Andersson, U., Henriksson, E., Ström, K., Alenfall, J., Göransson, O. and Holm, C. (2011) Rose hip exerts anti-diabetic effects via a mechanism involving down-regulation of the hepatic lipogenic program. Am. J. Physiol.-Metab and Endocrin. 300: E111.
- Andersson, U., Berger, K., Högberg, A., Landin-Olsson, M. and Holm, C. (2012) Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized double-blind cross-over investigation in obese persons. Eur. J. Clin. Nutr. 66:585.
- Heyman-Lindén, L., Seki, Y., Strom, P., Jones, HA, Charron, MJ, Berger, K. and Holm, C. (2016) Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet. J. Nutr. Biochem. Jan 27: 79-95.
- Larsson, S., Jones, HA, Göransson, O., Degerman, E. and Holm, C. (2016) Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase. Cell. Signal 3: 204-2013.