Kbtbd11 gene expression in adipose tissue increases in response to feeding and affects adipocyte differentiation

Abstract

Aims/Introduction The putative tumor suppressor gene, KBTBD11 , might play a role in tumorigenesis, and is associated with cellular apoptosis and proliferation in colorectal cancer cells. However, the function of Kbtbd11 during adipogenesis is unknown. The aim of the present study was to investigate the role of Kbtbd11 in the differentiation of 3T3‐L1 preadipocytes. Materials and Methods For the fasting–refeeding protocol, mice were subjected to fasting for 24 h, followed by a chow diet for 12 h. Adenovirus infection methods were used to examine the effect of Kbtbd11 , and 3T3‐L1 cells were analyzed with Oil Red O staining and real‐time polymerase chain reaction. Results The white adipose tissue expression of Kbtbd11 messenger ribonucleic acid (mRNA) was significantly higher in the re‐fed state than in the fasted state. Kbtbd11 mRNA levels were markedly increased in epididymal white adipose tissue of diet‐induced obesity mice compared with those in the mice fed a chow diet. In addition, Kbtbd11 mRNA expression was increased in a differentiation‐dependent manner in 3T3‐L1 cells. Knockdown of Kbtbd11 mRNA through the infection with adenoviral vectors remarkably inhibited triglyceride accumulation and adipocyte differentiation in 3T3‐L1 cells. In contrast, the overexpression of Kbtbd11 promoted the differentiation of 3T3‐L1 adipocytes. Conclusions The present findings show that Kbtbd11 expression might be involved in nutritional regulation and is increased in obese adipose tissue. In addition, Kbtbd11 appears to be required for the differentiation of adipocytes in 3T3 ‐ L1 cells. Collectively, these results show a novel link between the expression of Kbtbd11 and fat accumulation, and suggest that Kbtbd11 is a new therapeutic target for obesity.

A novel upstream transcription factor 1 target gene N4bp2l1 that regulates adipogenesis

“…After incubation for 48 h, the medium was changed to high-glucose DMEM containing 5 μg/mL insulin. The medium was changed every alternate day [8]. In experiments with adenovirus, 3T3-L1 cells were infected with adenovirus at day 2 before the induction of differentiation.…”

“…However, more studies are required to identify novel regulators of adipogenesis and the appropriate targets for anti-obesity drugs for the treatment of obesity pathogenesis. The 3T3-L1 preadipocyte is a well-established model for investigating mechanisms underlying adipocyte proliferation, differentiation, and lipid metabolism and is appropriate for the identification of genes that regulate adipocyte physiology, including adipogenesis [[6], [7], [8]].…”

Kbtbd11 contributes to adipocyte homeostasis through the activation of upstream stimulatory factor 1

“…The BTB/POZ domain functions as the protein–protein interaction domain to facilitate dimer formation and interaction with nonBTB domain comprising proteins, involving activities such as transcriptional regulation, cytoskeleton dynamics, ion channel assembly and gating, and protein ubiquitination/degradation [1]. The Kelch domain, which is widely conserved in mammals and insects, usually comprises 2–7 repeats of four-stranded beta-sheet motifs that form the beta-propeller structure [2]. The Kelch β-propellers primarily function as scaffolds for protein–protein interactions.…”

“…We have previously reported that Kbtbd11 is involved in nutritional regulation and is highly expressed in the epididymal white adipose tissue (eWAT) in diet-induced obesity (DIO) mice compared with that in mice fed on chow diet [2]. In addition, the adenovirus-mediated knockdown of Kbtbd11 in 3T3-L1 cells inhibits mitotic clonal expansion (MCE), which is required during the early stages of 3T3-L1 adipocyte differentiation [2]. In contrast, Kbtbd11 -overexpressing 3T3-L1 promotes MCE, which leads to the expression of adipocyte differentiation markers —C/ebpa and Pparg , and induces lipid accumulation [2], suggesting that Kbtbd11 expression levels play a major role in MCE and influence triglyceride accumulation and adipocyte differentiation.…”

“…In addition, the adenovirus-mediated knockdown of Kbtbd11 in 3T3-L1 cells inhibits mitotic clonal expansion (MCE), which is required during the early stages of 3T3-L1 adipocyte differentiation [2]. In contrast, Kbtbd11 -overexpressing 3T3-L1 promotes MCE, which leads to the expression of adipocyte differentiation markers —C/ebpa and Pparg , and induces lipid accumulation [2], suggesting that Kbtbd11 expression levels play a major role in MCE and influence triglyceride accumulation and adipocyte differentiation. In this context, the present study aimed to clarify the transcriptional regulation of Kbtbd11 to elucidate the functions underlying the role of Kbtbd11 in adipocyte differentiation.…”