Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion

Biochem Biophys Res Commun. 2014 Jul 18;450(1):318-23. doi: 10.1016/j.bbrc.2014.05.113. Epub 2014 Jun 2.

Abstract

ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and β-cell function. Elovl6 is expressed in both islets and β-cell lines. In mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture and β-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6(-/-) islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per β-cell and diabetes.

Keywords: Fatty acid; Insulin; Islet; Obesity; Type 2 diabetes; β-cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism*
  • Animals
  • Cells, Cultured
  • Dietary Fats / adverse effects*
  • Fatty Acid Elongases
  • Female
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / pathology*
  • Organ Specificity
  • Tissue Distribution

Substances

  • Dietary Fats
  • Elovl6 protein, mouse
  • Insulin
  • Acetyltransferases
  • Fatty Acid Elongases