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Eps8 – eat normal, stay thinner, live longer

Obesity is associated with an increased risk of numerous sequelae, such as type 2 diabetes, hypertension and cardiovascular diseases, collectively referred to as the metabolic syndrome, and cancer. The adipose tissue, far from only being a passive reservoir for the accumulation of lipids, is an endocrine organ that produces dozens of factors important for organism homeostasis. Excess adipose tissue can lead to the development of a systemic chronic inflammatory state that contributes to the development of obesity-associated morbidities.

Mice deficient for the Eps8 gene (Eps8KO) display reduced body weight, partial resistance to age- or diet-induced obesity, overall improved metabolic status and live longer than wild-type mice. Nina Offenhäuser wanted to identify the mechanisms behind this phenotype in collaboration with scientists from the German Mouse Clinic, in particular the energy metabolism, clinical chemistry and gene expression screens.

Reduction in both fat and lean mass in young and, even more pronounced, in aged Eps8KO mice lead to reduced body weight. Lower body weight was not caused by reduced food intake but  it was correlated with decreased intestinal nutrient absorption due to reduced intestinal microvilli length. An analysis of the subcellular localization of Eps8 in intestinal cells suggested that Eps8 is localized in intestinal microvilli. Since microvilli serve to augment the absorptive surface of the intestine their reduction in Eps8KO mice explained the absorption defect and the calorie restriction phenotype observed in these animals. Wild-type mice subjected to food restriction and thus calorie restriction show an absolute reduction in both lean and fat mass, and a relatively higher proportional reduction of fat mass. In addition, calorie-restricted mice live longer and have reduced core body temperature. Notably, Eps8KO mice also show reduced body temperature and increased longevity.


Loss of the Actin Remodeler Eps8 Causes Intestinal Defects and Improved Metabolic Status in Mice “, Tocchetti et al., Plos one, (2010) Volume 5, Issue 3