Insulin Sensitive ObesityWednesday, September 8, 2010
This week, I am hosting Matthias Blüher, Professor of Endocrinology from the University of Leipzig, Germany, who yesterday, presented a seminar on the topic of “Insulin Sensitive Obesity” at the Alberta Diabetes Institute.
As most readers will know, excess weight is typically associated with insulin resistance, which has been suggested to be a major underlying factor in the development of the metabolic syndrome.
However, as Blüher and other have shown before, there is a significant subset of individuals with excess weight, who are quite insulin sensitive and lack any sign or evidence for metabolic abnormalities. These individuals have also been described as being “metabolically healthy obese”.
Blüher’s group in Leipzig has performed extensive studies on this interesting group of subjects, which make up around 10-25% of individuals with severe obesity.
Using euglycemic insulin clamp studies (the gold-standard for measuring insulin sensitivity), Blüher and colleagues identified 30 individuals with typical insulin resistance and 30 individuals with atypical insulin sensitivity – both groups of subjects had a mean BMI of around 45 or severe obesity.
Among the many differences between the two groups, the best predictor of insulin resistance included more liver fat and increased visceral fat.
As reported previously, insulin resistant individuals had higher levels of glucose, HbA1c (although diabetic patients were excluded from the study), lower levels of HDL choldesterol, higher levels of CRP, larger adipocytes, greater macrophage infiltration of adipose tissue, and a higher leptin-to-adiponectin ratio.
Expression studies on fat tissue from both groups showed higher expression of various adipokines and biomarkers including AGT, MCP-1, PAI-1, Nampt (visfatin) endocannabinoids, ceramide, and oxidative stress in the insulin resistant group than the insulin sensitive controls.
In contrast, adipose tissue of the insulin sensitive subjects expressed higher levels of FTO, UCP-1, and adiponectin.
Blüher and colleagues were particularly thrilled to also see increased expression of vaspin (Visceral adipose tissue – derived serpin A12) in the insulin sensitive group, an enzyme that has been shown to increase insulin sensitivity and reduce food intake in animal studies. This molecule may provide a “drugable” target for treating obesity or related metabolic complications in the future.
Much of this work was undertaken as part of the newly funded Integrated Research and Management Centre for Obesity, which was recently funded by the German federal government in Leipzig.
As we discussed during Blüher’s meeting, we very much look forward to developing and expanding collaborations between the University of Alberta and the University of Leipzig as part of the recently negotiated Alberta-Saxony cooperation agreement.
I certainly look forward to working closely with Blüher and his colleagues over the coming years.
Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M, & Blüher M (2010). Insulin-sensitive obesity. American journal of physiology. Endocrinology and metabolism, 299 (3) PMID: 20570822