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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Diluted serum from calorie-restricted animals promotes mitochondrial -cell adaptations and protect against glucolipotoxicity

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Author(s):
Cerqueira, Fernanda M. [1, 2, 3] ; Chausse, Bruno [1] ; Baranovski, Boris M. [2] ; Liesa, Marc [3, 4] ; Lewis, Eli C. [2] ; Shirihai, Orian S. [2, 3, 4] ; Kowaltowski, Alicia J. [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Dept Bioquim, BR-05508 Sao Paulo - Brazil
[2] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem & Pharmacol, IL-84105 Beer Sheva - Israel
[3] Boston Univ, Sch Med, Dept Med, 715 Albany St, Boston, MA 02218 - USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, UCLA Sect Endocrinol, Los Angeles, CA 90095 - USA
Total Affiliations: 4
Document type: Journal article
Source: FEBS Journal; v. 283, n. 5, p. 822-833, MAR 2016.
Web of Science Citations: 10
Abstract

beta-cells quickly adjust insulin secretion to oscillations in nutrients carried by the blood, acting as fuel sensors. However, most studies of -cell 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-restricted rats versus serum from rats fed ad libitum, diluted tenfold in the medium, which did not contribute significantly to the pool of nutrients, on -cell mitochondrial function and dynamics under regular and high-nutrient culture conditions. Insulin secreting beta-cell derived line (INS1) cells incubated with serum from calorie-restricted rats (CR serum) showed higher levels of peroxisome proliferator-activated receptor gamma coactivator 1- (PGC-1) and active nitric oxide synthase. The expression of mitofusin-2 (Mfn-2) and optic atrophy 1 (OPA-1), proteins involved in mitochondrial fusion, was increased, while the levels of the mitochondrial fission mediator dynamin related protein 1 (DRP-1) were reduced. Consistent with changes in mitochondrial dynamics protein levels, CR serum treatment increased mitochondrial fusion rates, as well as their length and connectivity. These changes in mitochondrial morphology were associated with prolonged glucose-stimulated insulin secretion and mitochondrial respiration. When combining CR serum and high levels of glucose and palmitate (20 and 0.4 mm, respectively), an in vitro model of type II diabetes, we observed that signaling promoted by CR serum was enough to overcome glucolipotoxicity, as indicated by CR-mediated prevention of mitochondrial fusion arrest and reduced respiratory function in INS1 cells under glucolipotoxicity. Overall, our results provide evidence that non-nutrient factors in serum have a major impact on -cell mitochondrial adaptations to changes in metabolism. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC