Cardiometabolic Risk and Visceral Fat Remodeling in Subjects with Metabolic Syndrome

The obesity crisis in the world has been associated with an alarming increase in the prevalence of the metabolic syndrome disease cluster. The metabolic syndrome is particularly prevalent in visceral obesity, probably because visceral adipocytes supply free fatty acid (FFA) more largely than subcutaneous adipocytes [1,2]. Excess supply of FFA may cause a failure of a system of intracellular lipid homeostasis in remote organs [3-5], where normally adipocyte-derived leptin and adiponectin regulate oxidation of surplus liquids by activating fatty acid oxidation and by decreasing lipogenic enzymes [6-13]. If one can reduce visceral fat or switch fat distribution from subcutaneous to visceral, total cardiometabolic risk would be diminished by confining the lipid overload to cells specifically designed to store large quantities of surplus calories, subcutaneous white adipocytes.

Telmisartan, an angiotensin II type 1 receptor blocker, has a partial agonistic property for peroxisome proliferators-activated receptor-γ (PPARγ), which is a key regulator of adipocyte differentiation and function. We recently measured impact of telmisartan on fat distribution and insulin sensitivity in subjects with the metabolic syndrome [14]. In this open-label, prospective, randomized study, hypertensive patients with the metabolic syndrome were treated either with a calcium channel blocker or with telmisartan for 24 weeks. Systolic and diastolic blood pressure was decreased in both groups to a comparable level. But insulin and glucose levels during an oral 75 g glucose loading were decreased only in telmisartan group. Visceral fat area, determined by abdominal computed tomography scan, was reduced in telmisartan group after 24 weeks treatment, but subcutaneous fat area did not change in both groups.

The results imply that telmisartan could treat both the hemodynamic and metabolic aberrations seen in subjects with the metabolic syndrome, improving insulin resistance and glucose intolerance at least partly through visceral fat remodeling. Such visceral fat remodeling has been observed in pioglitaozone-treated patients [15], indicating that a shift of fat distribution from visceral to subcutaneous adipose depots is associated with improvements in hepatic and peripheral tissue sensitivity to insulin.

Reference

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Please address correspondence to:
Dr. Michio Shimabukuro
Second Department of Internal Medicine University of the Ryukyus
207 Uehara, Nishihara
Okinawa 903-0215, Japan
Tel: +81-98-895-1146
Fax: +81-98-944-3428
E-mail: mshimabukuro-ur[at]umin.ac.jp or me447945[at]members.interq.or.jp