| Title: |
Inflammation-linked adaptations in dermal microvascular reactivity accompany the development of obesity and type 2 diabetes |
| Authors: |
Nguyen-Tu, Marie-Sophie; Nivoit, Pierre; Oréa, Valérie; Lemoine, Sandrine; Acquaviva, Cécile; Pagnon-Minot, Aurélie; Fromy, Bérengère; Sethi, Jaswinder; Sigaudo-Roussel, D. |
| Contributors: |
Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique (LBTI); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS); Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN); Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon); Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM); Centre de Biologie et de Pathologie Est - CBPE; NOVOTEC; University of Southampton; M.-S.N.-T. was supported by the University of Lyon 1 and the study was supported by a grant from Fondation Lyon 1 and from DEFISENS-TACT MI CNRS. J.K.S. was supported by the British Heart Foundation (Award number PG/10/038/28359) and funded by the Wellcome Trust (Grant number 206453/Z/17/Z).; We thank Jocelyne Vial (Anexpeau facility, Lyon) for her kind help in treating the animals and we are very grateful to Nicolas Gadot (Anipath facility, Lyon). |
| Source: |
ISSN: 0307-0565. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2019 |
| Collection: |
HAL Lyon 1 (University Claude Bernard Lyon 1) |
| Subject Terms: |
MESH: Adiponectin; MESH: Adipose Tissue; White; MESH: Animals; MESH: Cytokines; MESH: Diabetes Mellitus; Experimental; Type 2; MESH: Inflammation; MESH: Male; MESH: Mice; Inbred C57BL; Obese; MESH: Microvessels; MESH: Obesity; MESH: Vasodilation; [SDV.BA]Life Sciences [q-bio]/Animal biology; [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Description: |
International audience ; Background/ObjectivesThe increased prevalence of obesity has prompted great strides in our understanding of specific adipose depots and their involvement in cardio-metabolic health. However, the impact of obesity on dermal white adipose tissue (dWAT) and dermal microvascular functionality remains unclear. This study aimed to investigate the temporal changes that occur in dWAT and dermal microvascular functionality during the development of diet-induced obesity and type 2 diabetes in mice.MethodsMetabolic phenotyping of a murine model of hypercaloric diet (HCD)-induced obesity and type 2 diabetes was performed at three time points that reflected three distinct stages of disease development; 2 weeks of HCD-overweight-metabolically healthy, 4 weeks of HCD-obese-prediabetic and 12 weeks of HCD-obese-type 2 diabetic mice. Expansion of dWAT was characterized histologically, and changes in dermal microvascular reactivity were assessed in response to pressure and the vasodilators SNP and Ach.ResultsHCD resulted in a progressive expansion of dWAT and increased expression of pro-inflammatory markers (IL1β and COX-2). Impairments in pressure-induced (PIV) and Ach-induced (endothelium-dependent) vasodilation occurred early, in overweight-metabolically healthy mice. Residual vasodilatory responses were NOS-independent but sensitive to COX inhibition. These changes were associated with reductions in NO and adiponectin bioavailability, and rescued by exogenous adiponectin or hyperinsulinemia. Obese-prediabetic mice continued to exhibit impaired Ach-dependent vasodilation but PIV appeared normalized. This normalization coincided with elevated endogenous adiponectin and insulin levels, and was sensitive to NOS, COX and PI3K, inhibition. In obese-type 2 diabetic mice, both Ach-stimulated and pressure-induced vasodilatory responses were increased through enhanced COX-2-dependent prostaglandin response.ConclusionsWe demonstrate that the development of obesity, metabolic dysfunction and type 2 diabetes, in ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/30006585; PUBMED: 30006585; PUBMEDCENTRAL: PMC6223541 |
| DOI: |
10.1038/s41366-018-0148-4 |
| Availability: |
https://hal.science/hal-02108186; https://hal.science/hal-02108186v1/document; https://hal.science/hal-02108186v1/file/s41366-018-0148-4.pdf; https://doi.org/10.1038/s41366-018-0148-4 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.819C4F07 |
| Database: |
BASE |