This review highlights the inflammatory and insulin-antagonizing effects of saturated fatty acids (SFA), which contribute to the development of metab

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.

Recent data suggest that proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. However, characterization of the cell types involved in inflammation and how these cells promote insulin resistance in human adipocytes are unclear. We simulated acute inflammation using the endotoxin lipopolysaccharide (LPS) to define the roles of nonadipocytes in primary cultures of human adipocytes. LPS induction of the mRNA levels of proinflammatory cytokines (e.g. IL-6, TNF-α, and IL-1β) and chemokines (e.g. IL-8, monocyte chemoattractant protein-1) occurred primarily in the nonadipocyte fraction of newly differentiated human adipocytes. Nonadipocytes were characterized as preadipocytes based on their abundant mRNA levels of preadipocyte markers preadipocyte factor-1 and adipocyte enhancer protein-1 and only trace levels of markers for macrophages and myocytes. The essential role of preadipocytes in inflammation was confirmed by modulating the degree of differentiation in the cultures from approximately 0–90%. LPS-induced proinflammatory cytokine/chemokine expression and nuclear factor-κB and MAPK signaling decreased as differentiation increased. LPS-induced cytokine/chemokine expression in preadipocytes was associated with: 1) decreased adipogenic gene expression, 2) decreased ligand-induced activation of a peroxisome proliferator activated receptor (PPAR)-γ reporter construct and increased phosphorylation of PPARγ, and 3) decreased insulin-stimulated glucose uptake. Collectively, these data demonstrate that LPS induces nuclear factor-κB- and MAPK-dependent proinflammatory cytokine/chemokine expression primarily in preadipocytes, which triggers the suppression of PPARγ activity and insulin responsiveness in human adipocytes.

Background: Quercetin and trans-resveratrol (trans-RSV) are plant polyphenols reported to reduce inflammation or insulin resistance associated with o