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

• Published in: Biochemical and biophysical research communications 2014-07, Vol.450 (1), p.318-323
• Main Authors: Tang, Nie, Matsuzaka, Takashi, Suzuki, Marii, Nakano, Yuta, Zao, Hui, Yokoo, Tomotaka, Suzuki-Kemuriyama, Noriko, Kuba, Motoko, Okajima, Yuka, Takeuchi, Yoshinori, Kobayashi, Kazuto, Iwasaki, Hitoshi, Yatoh, Shigeru, Takahashi, Akimitsu, Suzuki, Hiroaki, Sone, Hirohito, Shimada, Masako, Nakagawa, Yoshimi, Yahagi, Naoya, Yamada, Nobuhiro, Shimano, Hitoshi
• Format: Article
• Language: English
• Subjects: Acetyltransferases - metabolism; Animals; Cells, Cultured; Dietary Fats - adverse effects; Fatty acid; Female; Insulin; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Islet; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Mice; Mice, Knockout; Obesity; Obesity - etiology; Obesity - metabolism; Obesity - pathology; Organ Specificity; Tissue Distribution; Type 2 diabetes; β-cell
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.05.113

•Elovl6 is expressed in both islets and β-cell lines.•The obesity-induced islet hypertrophy was attenuated in Elovl6−/− mice.•Absence of Elovl6 increased GSIS of the islets from the HFHS diet-fed mice.•Absence of Elovl6 increased the ATP/ADP ratio and decreased ATF-3 expression. 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.