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However, most studies of \u03b2\u2010cell responses to nutrients do not discriminate between fuel levels and signaling components present in the circulation. Here we studied the effect of serum from calorie\u2010restricted rats versus serum from rats fed <jats:italic>ad libitum<\/jats:italic>, diluted tenfold in the medium, which did not contribute significantly to the pool of nutrients, on \u03b2\u2010cell mitochondrial function and dynamics under regular and high\u2010nutrient culture conditions. Insulin secreting beta\u2010cell derived line (<jats:styled-content style=\"fixed-case\">INS<\/jats:styled-content>1) cells incubated with serum from calorie\u2010restricted rats (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> serum) showed higher levels of peroxisome proliferator\u2010activated receptor gamma coactivator 1\u2010\u03b1 (PGC\u20101\u03b1) and active nitric oxide synthase. The expression of mitofusin\u20102 (Mfn\u20102) and optic atrophy 1 (<jats:styled-content style=\"fixed-case\">OPA<\/jats:styled-content>\u20101), proteins involved in mitochondrial fusion, was increased, while the levels of the mitochondrial fission mediator dynamin related protein 1 (<jats:styled-content style=\"fixed-case\">DRP<\/jats:styled-content>\u20101) were reduced. Consistent with changes in mitochondrial dynamics protein levels, <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> serum treatment increased mitochondrial fusion rates, as well as their length and connectivity. These changes in mitochondrial morphology were associated with prolonged glucose\u2010stimulated insulin secretion and mitochondrial respiration. When combining <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> serum and high levels of glucose and palmitate (20 and 0.4 m<jats:sc>m<\/jats:sc>, respectively), an <jats:italic>in vitro<\/jats:italic> model of type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> diabetes, we observed that signaling promoted by <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> serum was enough to overcome glucolipotoxicity, as indicated by <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010mediated prevention of mitochondrial fusion arrest and reduced respiratory function in <jats:styled-content style=\"fixed-case\">INS<\/jats:styled-content>1 cells under glucolipotoxicity. Overall, our results provide evidence that non\u2010nutrient factors in serum have a major impact on \u03b2\u2010cell mitochondrial adaptations to changes in metabolism.<\/jats:p>","DOI":"10.1111\/febs.13632","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T06:50:53Z","timestamp":1452063053000},"page":"822-833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Diluted serum from calorie\u2010restricted animals promotes mitochondrial \u03b2\u2010cell adaptations and protect against glucolipotoxicity"],"prefix":"10.1111","volume":"283","author":[{"given":"Fernanda M.","family":"Cerqueira","sequence":"first","affiliation":[{"name":"Department of Medicine Boston University School of Medicine MA USA"},{"name":"Department of Clinical Biochemistry and Pharmacology Faculty of Health Sciences Ben\u2010Gurion University of the Negev Israel"},{"name":"Departamento de Bioqu\u00edmica 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