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CDKN2C expression in adipose tissue is reduced in type II diabetes and central obesity: impact on adipocyte differentiation and lipid storage?

Pereira, Maria J., 1981- (författare)
Uppsala universitet,Klinisk diabetologi och metabolism
Vranic, Milica (författare)
Uppsala universitet,Klinisk diabetologi och metabolism
Kamble, Prasad G. (författare)
Uppsala universitet,Klinisk diabetologi och metabolism
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Jernow, Henning (författare)
Uppsala universitet,Institutionen för medicinska vetenskaper,Clinical Diabetes and Metabolism
Kristofi, Robin (författare)
Uppsala universitet,Klinisk diabetologi och metabolism
Holbikova, E. M. A. (författare)
Uppsala universitet,Institutionen för medicinska vetenskaper
Skrtic, Stanko, 1970 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
Kullberg, Joel, 1979- (författare)
Uppsala universitet,Geriatrik,Radiologi
Svensson, Maria K. (författare)
Uppsala universitet,Klinisk diabetologi och metabolism,Njurmedicin
Hetty, Susanne, PhD, 1979- (författare)
Uppsala universitet,Klinisk diabetologi och metabolism,Jämförande fysiologi,Science for Life Laboratory, SciLifeLab
Eriksson, Jan (författare)
Uppsala universitet,Klinisk diabetologi och metabolism
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 (creator_code:org_t)
Elsevier BV, 2022
2022
Engelska.
Ingår i: Translational Research. - : Elsevier BV. - 1931-5244 .- 1878-1810. ; 242, s. 105-121
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. Functional studies included adipocyte glucose uptake and lipolysis rates. CRISPR/Cas9 CDKN2C gene knockdown was performed in human preadipocytes to assess adipogenesis. CDKN2C mRNA expression in SAT and OAT was reduced in T2D and obese subjects compared to controls. CDKN2C expression in SAT was inversely correlated with measures of hyperglycemia, insulin resistance and visceral adiposity and positively correlated with expression of genes in several metabolic pathways, including insulin signaling and fatty acid and carbohydrate metabolism. CDKN2C protein was mainly expressed in adipocytes compared to stromal vascular cells, and its gene and protein expression was up-regulated during adipocyte differentiation. Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage. © 2021 The Authors

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

ADIPOQ=Adiponectin
AT=Adipose tissue
CDKN2C=Cyclin-Dependent Kinase Inhibitor 2C
CEBPA=CCAAT Enhancer Binding Protein Alpha
FASN=Fatty Acid Synthase
GWAS=Genome-wide association study
MRI=Magnetic resonance imaging
OAT=Omental adipose tissue
PPARG=Peroxisome Proliferator-Activated Receptor Gamma
RNP=Ribonucleoprotein
SAT=Subcutaneous adipose tissue
sgRNA=Single-guide RNA
SVF=Stromal vascular fraction
T2D=Type II diabetes
VAT=Visceral adipose tissue
WHR=Waist-hip ratio

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