Mouse models of the metabolic syndrome

Abstract

The metabolic syndrome (MetS) is characterized by obesity concomitant with other metabolic abnormalities such as hypertriglyceridemia, reduced high-density lipoprotein levels, elevated blood pressure and raised fasting glucose levels. The precise definition of MetS, the relationships of its metabolic features, and what initiates it, are debated. However, obesity is on the rise worldwide, and its association with these metabolic symptoms increases the risk for diabetes and cardiovascular disease (among many other diseases). Research needs to determine the mechanisms by which obesity and MetS increase the risk of disease. In light of this growing epidemic, it is imperative to develop animal models of MetS. These models will help determine the pathophysiological basis for MetS and how MetS increases the risk for other diseases. Among the various animal models available to study MetS, mice are the most commonly used for several reasons. First, there are several spontaneously occurring obese mouse strains that have been used for decades and that are very well characterized. Second, high-fat feeding studies require only months to induce MetS. Third, it is relatively easy to study the effects of single genes by developing transgenic or gene knockouts to determine the influence of a gene on MetS. For these reasons, this review will focus on the benefits and caveats of the most common mouse models of MetS. It is our hope that the reader will be able to use this review as a guide for the selection of mouse models for their own studies.

Fig. 1.

Lipoprotein profiles different models. Lipoproteins were separated from plasma by running 100 μl over a Superose 6 column at a flow rate of 0.5 ml/min in buffer containing 0.15 M NaCl, 0.01 M Na₂HPO₄ and 1 mM EDTA. Forty 0.5 ml fractions were collected, and the cholesterol concentration in fractions 10–40 was assessed. Typically, VLDL elutes in fractions 15–20, LDL in fractions 21–27, and HDL in fractions 28–34. (A) Lipoprotein profiles comparing a ‘normal’ human profile with a C57BL/6J profile. (B) C57BL/6J and LepR^db/db mice. The LDL/HDL1 peak elutes in fractions 23–27. (C) Lipoprotein profiles of lean LDLR^−/− and apoE^−/− mice. (D) Lipoprotein profiles of obese LDLR^−/− and apoE^−/− mice.