M1 macrophage subtypes activation and adipocyte dysfunction worsen during prolonged consumption of a fructose rich diet

GAMBARO, SE; ZUBIRIA, MG; PORTALES, A; REY, MA; RUMBO, M; GIOVAMBATTISTA, ANDRÉS

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ELSEVIER SCIENCE INC

Año: 2018

0955-2863

Fructose rich diet (FRD) has been associated with obesity development, which ischaracterized by adipocytes hypertrophy and chronic low-grade inflammation. Interaction ofadipocytes and immune cells play a key role in adipose tissue (AT) alterations in obesity. Weassessed the metabolic and immune impairments in AT in a murine obesity model inducedby FRD at different periods. Adult Swiss mice were divided into groups of 6 and 10 weeks offructose (FRD 6wk, FRD 10wk) or water intake (CTR 6wk, CTR 10wk). FRD induced increasedin body weight, epidydimal AT mass, plasmatic and liver Tg, and impaired insulin sensitivity.Also, hypertrophic adipocytes from FRD 6wk-10wk mice showed higher IL-6 when stimulatedwith LPS and leptin secretion. Several of these alterations worsened in FRD 10wk. RegardingAT inflammation, FRD mice have increased TNFα, IL-6, IL1β, and decrease in IL-10, CD206mRNA levels. Using CD11b, LY6C, CD11c and CD206 as macrophages markers, we identifiedfor first time in AT M1 (M1a: Ly6C+/-CD11c+CD206- and M1b: Ly6C+/-CD11c+CD206+) andM2 subtypes (Ly6C+/-CD11c-CD206+). M1a phenotype increased from 6 weeks onward,while Ly6C+/- M1b phenotype increased only after 10 weeks. Finally, co-culture ofRAW264.7 (monocytes cell line) and CTR or FRD adipocytes showed that FRD 10wkadipocytes increased IL-6 expression in non- or LPS-stimulated monocytes. Our resultsshowed that AT dysfunction got worse as the period of fructose consumption was longer.Inflammatory macrophage subtypes increased depending on the period of FRD intake andhypertrophic adipocytes were able to create an environment that favored M1 phenotype invitro.