Sandra López-Domènech1, Celia Bañuls2, Aranzazu M de Marañón1, Zaida Abab-Jiménez1, Carlos Morillas1, Segundo Ángel Gómez-Abril3, Susana Rovira-Llopis2, Víctor Manuel Víctor4, Antonio Hernández-Mijares5, Milagros Rocha6. 1. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain. 2. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Avda. Menéndez Pelayo 4, 46010 Valencia, Spain. 3. Service of General and Digestive Surgery, University Hospital Doctor Peset-FISABIO, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain. 4. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Avda. Menéndez Pelayo 4, 46010 Valencia, Spain; CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, University of Valencia, Av Blasco Ibáñez 13, 46010 Valencia, Spain; Department of Physiology, Faculty of Medicine, University of Valencia, Av Blasco Ibáñez 13, 46010 Valencia, Spain. 5. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Avda. Menéndez Pelayo 4, 46010 Valencia, Spain; Department of Medicine, Faculty of Medicine, University of Valencia, Av Blasco Ibáñez 13, 46010 Valencia, Spain. Electronic address: hernandez_antmij@gva.es. 6. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Avda. Menéndez Pelayo 4, 46010 Valencia, Spain; CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, University of Valencia, Av Blasco Ibáñez 13, 46010 Valencia, Spain. Electronic address: milagros.rocha@uv.es.
Abstract
BACKGROUND & AIMS: It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). METHODS: In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo study, a biopsy of VAT and SAT was removed from thirty-four obese patients and incubated with D-pinitol for 48 h. RESULTS: The consumption of a PEB reduced circulating levels of IL6 and TNFα and increased SIRT1 protein expression in PBMCs. Ex vivo experiments showed a decline in gene expression and protein levels of IL6 and TNFα in SAT and a reduction in ER stress parameters (ATF6 and CHOP), while VAT markers remained unaltered. Differential gene expression profiles revealed an up-regulation of SIRT1 and insulin-signaling pathways in SAT with respect to VAT. CONCLUSIONS: Our results suggests that pinitol down-regulates the inflammatory pathway which may lead to novel treatment options for obesity and its metabolic disorders.
BACKGROUND & AIMS: It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in humanobesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). METHODS: In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo study, a biopsy of VAT and SAT was removed from thirty-four obesepatients and incubated with D-pinitol for 48 h. RESULTS: The consumption of a PEB reduced circulating levels of IL6 and TNFα and increased SIRT1 protein expression in PBMCs. Ex vivo experiments showed a decline in gene expression and protein levels of IL6 and TNFα in SAT and a reduction in ER stress parameters (ATF6 and CHOP), while VAT markers remained unaltered. Differential gene expression profiles revealed an up-regulation of SIRT1 and insulin-signaling pathways in SAT with respect to VAT. CONCLUSIONS: Our results suggests that pinitol down-regulates the inflammatory pathway which may lead to novel treatment options for obesity and its metabolic disorders.
Authors: Robin Bonomi; Vadim Popov; Maxwell T Laws; David Gelovani; Anjoy Majhi; Aleksandr Shavrin; Xin Lu; Otto Muzik; Nashaat Turkman; Renshyan Liu; Thomas Mangner; Juri G Gelovani Journal: J Med Chem Date: 2018-08-13 Impact factor: 7.446