Baldini 2021 Life Sci
|Baldini F, Fabbri R, Eberhagen C, Voci A, Portincasa P, Zischka H, Vergani L (2021) Adipocyte hypertrophy parallels alterations of mitochondrial status in a cell model for adipose tissue dysfunction in obesity. Life Sci 265:118812.|
Baldini Francesca, Fabbri Rita, Eberhagen Carola, Voci Adriana, Portincasa Piero, Zischka Hans, Vergani Laura (2021) Life Sci
Abstract: Adipocyte hypertrophy is the main cause of obesity. A deeper understanding of the molecular mechanisms regulating adipocyte dysfunction may help to plan strategies to treat/prevent obesity and its metabolic complications. Here, we investigated in vitro the molecular alterations associated with early adipocyte hypertrophy, focusing on mitochondrial dysfunction.
As model of adipocyte hypertrophy, we employed 3T3-L1 preadipocytes firstly differentiated into mature adipocytes, then cultured with long-chain fatty acids. As a function of differentiation and hypertrophy, we assessed triglyceride content, lipid droplet size, radical homeostasis by spectrophotometry and microscopy, as well as the expression of PPARγ, adiponectin and metallothioneins. Mitochondrial status was investigated by electron microscopy, Oxygraph-2k (O2K) high-resolution respirometry, fluorimetry and western blot.
Compared to mature adipocytes, hypertrophic adipocytes showed increased triglyceride accumulation and lipid peroxidation, larger or unique lipid droplet, up-regulated expression of PPARγ, adiponectin and metallothioneins. At mitochondrial level, early-hypertrophic adipocytes exhibited: (i) impaired mitochondrial oxygen consumption with parallel reduction in the mitochondrial complexes; (ii) no changes in citrate synthase and HSP60 expression, and in the inner mitochondrial membrane polarization; (iii) no stimulation of mitochondrial fatty acid oxidation. Our findings indicate that the content, integrity, and catabolic activity of mitochondria were rather unchanged in early hypertrophic adipocytes, while oxygen consumption and oxidant production were altered.
In the model of early adipocyte hypertrophy exacerbated oxidative stress and impaired mitochondrial respiration were observed, likely depending on reduction in the mitochondrial complexes, without changes in mitochondrial mass and integrity. • Keywords: Adipocyte hypertrophy, Mitochondria, Mitochondrial respiration, Obesity, Oxidative stress • Bioblast editor: Plangger M • O2k-Network Lab: DE Munich Zischka H
Labels: MiParea: Respiration Pathology: Obesity
Organism: Mouse Tissue;cell: Fibroblast Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k