M1 macrophages subtypes activation is related to the adipocyte dysfunction in epididymal adipose tissue and to the fructose rich diet period

GAMBARO SABRINA ELIANA; ZUBIRÍA, MARÍA GUILLERMINA; PORTALES, ANDREA; REY, MARÍA AMANDA; RUMBO, MARTIN; GIOVAMBATTISTA, ANDRÉS

Ciudad del Cabo

Congreso; 18th International Congress of Endocrinology; 2018

International Society of Endocrinology

The increasing prevalence of obesity over the world has become one of the main public health problems and is usually related to unbalanced diet such as fructose rich diet (FRD). FRD are characterized by hypertrophic adipocytes and chronic low-grade inflammation. Adipocytes and immune cells interaction play a key role in adipose tissue (AT) alterations in obesity. The aim of this study was to assess the metabolic and immune impairments in AT induced by FRD at different periods. Adults Swiss mice were given FRD for 6 or 10 weeks (FRD6wk, FRD10wk) or water (CTR6wk, CTR10wk). Induced increment in body weight, epidydimal AT mass and plasmatic Tg. Also, hypertrophic adipocytes from FRD6wk-10wk mice showed higher IL-6 when stimulated with LPS. Several of these alterations worsened in FRD10wk. Regarding AT inflammation, FRD induced an increment in mRNA of TNFα, IL-6, IL1β and decrease in IL-10, CD206. We were able to identify for first time in AT M1 subtypes (M1a: Ly6C+/-CD11c+CD206- and M1b: Ly6C+/-CD11c+CD206+) and M2 (Ly6C+/-CD11c-CD206+). FRD induced an increment in M1a phenotype since 6weeks while Ly6C+/- M1b phenotype increased only in FRD10wk. Finally, co-culture of RAW264.7 (monocytes) and CTR or FRD adipocytes showed that FRD10wk adipocytes were able to increment IL-6 expression in non-or LPS stimulated monocyte. In conclusion, our results showed that AT dysfunction got worse with the period of fructose consumption. The inflammatory macrophages subtypes were increased depending the period of FRD and that the adipocytes from FRD10wk were able to create an environment that favored M1 phenotype in vitro.