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- Bean 2016 Abstract Mito Xmas Meeting Innsbruck + (Mitochondria-shaping proteins modulate bio … Mitochondria-shaping proteins modulate bioenergetics, apoptosis, Ca<sup>2+</sup> signalling and autophagy. The inner membrane pro-fusion and cristae shaping protein Optic atrophy 1 (Opa1) protects multiple tissues from damage by regulating cytochrome c release and mitochondrial respiratory efficiency, but whether this is mirrored by systemic changes in intermediary metabolism is unknown. Here we identify Opa1 as a key regulator of insulin sensitivity and adipose tissue function. Controlled Opa1 overexpression in the mouse reduces weight, improves glucose metabolism and insulin sensitivity, by reducing fat depots and favoring brownization of white adipose cells ''in vivo'' and ''in vitro''. Adipocyte-specific Opa1 deletion triggers a lipodystrophic phenotype with hyperglycemia, insulin resistance, brown adipose tissue whitening and hepatosteatosis. Our findings identify the genetic and metabolic basis for Opa1 role in a lean and insulin-sensitive phenotype, paving the way for novel therapeutic strategies to treat obesity and diabetes. therapeutic strategies to treat obesity and diabetes.)
