Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes
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Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes. / Agrawal, Madhur; Yeo, Chia Rou; Shabbir, Asim; Chhay, Vanna; Silver, David L; Magkos, Faidon; Vidal-Puig, Antonio; Toh, Sue-Anne.
In: F A S E B Journal, Vol. 33, No. 1, 2019, p. 430-440.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes
AU - Agrawal, Madhur
AU - Yeo, Chia Rou
AU - Shabbir, Asim
AU - Chhay, Vanna
AU - Silver, David L
AU - Magkos, Faidon
AU - Vidal-Puig, Antonio
AU - Toh, Sue-Anne
N1 - (Ekstern)
PY - 2019
Y1 - 2019
N2 - Fat storage-inducing transmembrane protein 2 (FIT2) aids in partitioning of cellular triacylglycerol into lipid droplets. A genome-wide association study reported FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations. Mice with adipose tissue (AT)-specific FIT2 knockout exhibited lipodystrophic features, with reduced AT mass, insulin resistance, and greater inflammation in AT when fed a high-fat diet. The role of FIT2 in regulating human adipocyte function is not known. Here, we found FIT2 protein abundance is lower in subcutaneous and omental AT obtained from patients with T2DM compared with nondiabetic control subjects. Partial loss of FIT2 protein in primary human adipocytes attenuated their lipid storage capacity and induced insulin resistance. After palmitate treatment, triacylglycerol accumulation, insulin-induced Akt (Ser-473) phosphorylation, and insulin-stimulated glucose uptake were significantly reduced in FIT2 knockdown adipocytes compared with control cells. Gene expression of proinflammatory cytokines IL-18 and IL-6 and phosphorylation of the endoplasmic reticulum stress marker inositol-requiring enzyme 1α were greater in FIT2 knockdown adipocytes than in control cells. Our results show for the first time that FIT2 is associated with T2DM in humans and plays an integral role in maintaining metabolically healthy AT function.-Agrawal, M., Yeo, C. R., Shabbir, A., Chhay, V., Silver, D. L., Magkos, F., Vidal-Puig, A., Toh, S.-A. Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes.
AB - Fat storage-inducing transmembrane protein 2 (FIT2) aids in partitioning of cellular triacylglycerol into lipid droplets. A genome-wide association study reported FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations. Mice with adipose tissue (AT)-specific FIT2 knockout exhibited lipodystrophic features, with reduced AT mass, insulin resistance, and greater inflammation in AT when fed a high-fat diet. The role of FIT2 in regulating human adipocyte function is not known. Here, we found FIT2 protein abundance is lower in subcutaneous and omental AT obtained from patients with T2DM compared with nondiabetic control subjects. Partial loss of FIT2 protein in primary human adipocytes attenuated their lipid storage capacity and induced insulin resistance. After palmitate treatment, triacylglycerol accumulation, insulin-induced Akt (Ser-473) phosphorylation, and insulin-stimulated glucose uptake were significantly reduced in FIT2 knockdown adipocytes compared with control cells. Gene expression of proinflammatory cytokines IL-18 and IL-6 and phosphorylation of the endoplasmic reticulum stress marker inositol-requiring enzyme 1α were greater in FIT2 knockdown adipocytes than in control cells. Our results show for the first time that FIT2 is associated with T2DM in humans and plays an integral role in maintaining metabolically healthy AT function.-Agrawal, M., Yeo, C. R., Shabbir, A., Chhay, V., Silver, D. L., Magkos, F., Vidal-Puig, A., Toh, S.-A. Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes.
U2 - 10.1096/fj.201701321RR
DO - 10.1096/fj.201701321RR
M3 - Journal article
C2 - 30020828
VL - 33
SP - 430
EP - 440
JO - F A S E B Journal
JF - F A S E B Journal
SN - 0892-6638
IS - 1
ER -
ID: 210872919