Adipose cell size changes are associated with a drastic actin remodeling

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Adipose cell size changes are associated with a drastic actin remodeling. / Hansson, Björn; Morén, Björn; Fryklund, Claes; Vliex, Lars; Wasserstrom, Sebastian; Albinsson, Sebastian; Berger, Karin; Stenkula, Karin G.

I: Scientific Reports, Vol. 9, Nr. 1, 12941, 2019.

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T1 - Adipose cell size changes are associated with a drastic actin remodeling

AU - Hansson, Björn

AU - Morén, Björn

AU - Fryklund, Claes

AU - Vliex, Lars

AU - Wasserstrom, Sebastian

AU - Albinsson, Sebastian

AU - Berger, Karin

AU - Stenkula, Karin G.

PY - 2019

Y1 - 2019

N2 - Adipose tissue plays a major role in regulating whole-body insulin sensitivity and energy metabolism. To accommodate surplus energy, the tissue rapidly expands by increasing adipose cell size (hypertrophy) and cell number (hyperplasia). Previous studies have shown that enlarged, hypertrophic adipocytes are less responsive to insulin, and that adipocyte size could serve as a predictor for the development of type 2 diabetes. In the present study, we demonstrate that changes in adipocyte size correlate with a drastic remodeling of the actin cytoskeleton. Expansion of primary adipocytes following 2 weeks of high-fat diet (HFD)-feeding in C57BL6/J mice was associated with a drastic increase in filamentous (F)-actin as assessed by fluorescence microscopy, increased Rho-kinase activity, and changed expression of actin-regulating proteins, favoring actin polymerization. At the same time, increased cell size was associated with impaired insulin response, while the interaction between the cytoskeletal scaffolding protein IQGAP1 and insulin receptor substrate (IRS)-1 remained intact. Reversed feeding from HFD to chow restored cell size, insulin response, expression of actin-regulatory proteins and decreased the amount of F-actin filaments. Together, we report a drastic cytoskeletal remodeling during adipocyte expansion, a process which could contribute to deteriorating adipocyte function.

AB - Adipose tissue plays a major role in regulating whole-body insulin sensitivity and energy metabolism. To accommodate surplus energy, the tissue rapidly expands by increasing adipose cell size (hypertrophy) and cell number (hyperplasia). Previous studies have shown that enlarged, hypertrophic adipocytes are less responsive to insulin, and that adipocyte size could serve as a predictor for the development of type 2 diabetes. In the present study, we demonstrate that changes in adipocyte size correlate with a drastic remodeling of the actin cytoskeleton. Expansion of primary adipocytes following 2 weeks of high-fat diet (HFD)-feeding in C57BL6/J mice was associated with a drastic increase in filamentous (F)-actin as assessed by fluorescence microscopy, increased Rho-kinase activity, and changed expression of actin-regulating proteins, favoring actin polymerization. At the same time, increased cell size was associated with impaired insulin response, while the interaction between the cytoskeletal scaffolding protein IQGAP1 and insulin receptor substrate (IRS)-1 remained intact. Reversed feeding from HFD to chow restored cell size, insulin response, expression of actin-regulatory proteins and decreased the amount of F-actin filaments. Together, we report a drastic cytoskeletal remodeling during adipocyte expansion, a process which could contribute to deteriorating adipocyte function.

U2 - 10.1038/s41598-019-49418-0

DO - 10.1038/s41598-019-49418-0

M3 - Article

C2 - 31506540

AN - SCOPUS:85072029042

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12941

ER -