Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity

Jiazhen Tang, Hongyi Zhou, Khushboo Sahay, Wenqiong Xu, Jing Yang, Wei Zhang, Weiqin Chen

Research output: Contribution to journalArticle

Abstract

Background: Obesity and its associated morbidities represent the major and most rapidly expanding world-wide health epidemic. Recent genome-wide association studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated with waist–hip ratio (WHR) with adjustment for body mass index (BMI) (WHRadjBMI). However, the function of FAM13A in adipose development and obesity remains largely uncharacterized. Methods: The expression of FAM13A in adipose tissue depots were investigated using lean, genetic obese and high fat diet-induced obese (DIO) animal models and during adipocyte differentiation. Stromal vascular cells (SVCs) or 3T3-L1 cells with gain and loss of function of FAM13A were used to determine the involvement of FAM13A in regulating adipocyte differentiation. Adipose development and metabolic homeostasis in Fam13a−/− mice were characterized under normal chow and high fat diet feeding. Results: Murine FAM13A expression was nutritionally regulated and dramatically reduced in epididymal and subcutaneous fat in genetic and diet-induced obesity. Its expression was enriched in mature adipocytes and significantly upregulated during murine and human adipogenesis potentially through a peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent mechanism. However, Fam13a−/− mice only exhibited a tendency of higher adiposity and were not protected from DIO and insulin resistance. While Fam13a−/− SVCs maintained normal adipogenesis, overexpression of FAM13A in 3T3-L1 preadipocytes downregulated β-catenin signaling and rendered preadipocytes more susceptible to apoptosis. Moreover, FAM13A overexpression largely blocked adipogenesis induced by a standard hormone cocktail, but adipogenesis can be partially rescued by the addition of PPARγ agonist pioglitazone at an early stage of differentiation. Conclusions: Our results suggest that FAM13A is dispensable for adipose development and insulin sensitivity. Yet the expression of FAM13A needs to be tightly controlled in adipose precursor cells for their proper survival and downstream adipogenesis. These data provide novel insights into the link between FAM13A and obesity.

Original languageEnglish (US)
Pages (from-to)1269-1280
Number of pages12
JournalInternational Journal of Obesity
Volume43
Issue number6
DOIs
StatePublished - Jun 1 2019

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Adipogenesis
Insulin Resistance
Obesity
Adipocytes
PPAR gamma
pioglitazone
High Fat Diet
Stromal Cells
Blood Vessels
Diet
3T3-L1 Cells
Catenins
Genome-Wide Association Study
Subcutaneous Fat
Adiposity
Single Nucleotide Polymorphism
Adipose Tissue
Body Mass Index
Homeostasis
Down-Regulation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity. / Tang, Jiazhen; Zhou, Hongyi; Sahay, Khushboo; Xu, Wenqiong; Yang, Jing; Zhang, Wei; Chen, Weiqin.

In: International Journal of Obesity, Vol. 43, No. 6, 01.06.2019, p. 1269-1280.

Research output: Contribution to journalArticle

Tang, Jiazhen ; Zhou, Hongyi ; Sahay, Khushboo ; Xu, Wenqiong ; Yang, Jing ; Zhang, Wei ; Chen, Weiqin. / Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity. In: International Journal of Obesity. 2019 ; Vol. 43, No. 6. pp. 1269-1280.
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T1 - Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity

AU - Tang, Jiazhen

AU - Zhou, Hongyi

AU - Sahay, Khushboo

AU - Xu, Wenqiong

AU - Yang, Jing

AU - Zhang, Wei

AU - Chen, Weiqin

PY - 2019/6/1

Y1 - 2019/6/1

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