Focus on Obesity
In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, there are 4 articles of diverse scope on the topic of obesity. There has been an alarming increase in the prevalence of obesity in the US and the rest of the developed world. There also has been a parallel increase in the prevalence of type 2 diabetes mellitus (T2DM), which is expected to add to the burden of cardiovascular morbidity and mortality simply because macrovascular disease is the leading cause of death in T2DM. The current understanding of the mechanisms by which T2DM contributes to cardiovascular disease includes dyslipidemia, insulin resistance, which adversely affects multiple metabolic pathways in many cell types, and inflammation.
See accompanying articles on pages 186, 193, 200, and 327
Two of the articles in this issue focus on the role of inflammatory leukocytes in white and visceral adipose depots and the effects of these cells on systemic insulin resistance and glucose homeostasis. In Wu et al,1 the authors show that CD11c, a marker expressed on certain subsets of monocyte-derived cells, was increased in the visceral fat of obese humans, in adipose tissue in mice, and on circulating monocytes in both species. Furthermore, the circulating monocyte level of CD11c in humans was correlated with insulin resistance. That CD11c was not just a marker of cells having a high level of inflammation but also was integral to their adversely altered metabolic state was strongly suggested by the lower insulin resistance and better glucose tolerance in obese mice deficient in CD11c. The results hold out the exciting possibility of CD11c being a circulating marker of the severity of metabolic syndrome.
Ohmura et al2 provide new insights into the contributions of macrophage in adipose tissues to impaired insulin sensitivity and glucose homeostasis. In particular, their data argue for a pathological role of natural killer T cells. Obese mice deficient in natural killer T cells demonstrated less macrophage infiltration of adipose tissue and improved glucose homeostasis. Another novel angle represented in this issue is that of the impact of leptin on angiogenesis. Since its discovery as a master regulator of weight,3 the list of the metabolic effects of leptin has grown apace. Heida et al4 show that this list now includes angiogenesis. Notably, the obese state in humans prevented leptin’s stimulation of circulating angiogenic cells to form new blood vessels. As the authors note, the angiogenic and potentially vasculoprotective effects of leptin may be impaired in obese individuals.
The final article brings new insights from the application of genetic methods to the study of obesity and T2DM. He et al5 tap into the Nurses Health Study to look at the relationship between an obesity “genotype risk score” (a summing-up of a number of known obesity risk alleles) and the risk of cardiovascular disease in T2DM women. They found that there was increased cardiovascular disease risk in the subjects at the highest quartile of the genotype risk score, and that some of this risk was attributable to changes in known cardiovascular risk factors, such as high-density lipoprotein and adiponectin. This article makes the important point that obesity-predisposing variants relate to the susceptibility to T2DM. It is well-known that not all obese people have T2DM and increased risk of cardiovascular disease, so the results also suggest that there are still-to-be-discovered resistance genetic factors.
These interesting articles now join the ever-expanding literature on obesity. Given its increasing importance to many areas of medicine, more basic, translational, and clinical research efforts will be needed to formulate effective therapies for obesity. We look forward to participating in this goal by continuing to disseminate important work in obesity and cardiovascular disease.
Wu H, Perrard XD, Wang Q, Perrard J, Polsani V, Jones P, Smith CW, Ballantyne C. CD11c expression in adipose tissue and blood and its role in diet-induced obesity. 2010; 30: 186–192.
Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S, Andoh Y, Fujii S, Iwabuchi K, Onoe K, Tsutsui H. Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. 2010; 30: 193–199.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995; 269: 543–546.
Heida NM, Leifheit-Nestler M, Schroeter M, Mueller JP, Cheng IF, Henkel S, Limbourg A, Limbourg FP, Alves F, Quigley JP, Ruggeri ZM, Hasenfuss G, Konstantinides S, Schaefer K. Leptin enhances the potency of circulating angiogenic cells via Src kinase and integrin v5: implications for angiogenesis in human obesity. 2010; 30: 200–206.
He M, Cornelis MC, Franks PW, Zhang C, Hu FB, Qi L. Obesity genotype score and cardiovascular risk in women with type 2 diabetes. 2010; 30: 327–332.