The increasingly complex regulation of adipocyte differentiation

Poulos, Sylvia P.; Dodson, Michael V.; Culver, Melinda F; Hausman, Gary

doi:10.1177/1535370215619041

Cited by 40 publications

(44 citation statements)

References 82 publications

(131 reference statements)

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“…[25][26][27][28] Obesity is defined as an excessive accumulation of fat mass in WAT to the extent that health may be adversely affected, which can occur through an increase of adipocyte volume (hypertrophy), number (hyperplasia) or a combined form (hypertrophy-hyperplasia). 29,30 Therefore, the differentiation of adipocytes is of great importance for the physiological and pathophysiological function of adipose tissue. However, the role of HNF1b in adipocyte differentiation is unknown.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Wang

et al. 2017

Cell Death Differ

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Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression. Overexpression of PPARγ suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. HNF1b can directly bind with the promoter of PPARγ in 3T3-L1 cells, which was decreased after adipogenic differentiation. HNF1b promoted apoptotic and autophagic cell death in early differentiated adipocytes through regulation of cell cycle progress and cell death-related factors, and thus inhibited the process of mitotic clonal expansion (MCE). HNF1b acted as an antioxidant regulator through regulating various antioxidant enzymes via binding with antioxidant response element. Oxidant treatment suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. Overall, our results suggest that HNF1b is a novel negative regulator of adipocyte differentiation through regulation of PPARγ signaling, MCE and redox state.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Wang

et al. 2017

Cell Death Differ

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“…35,36 Thus, it appears that the protein status of these transcriptional factors, Values are expressed as means ± SD of six to eight rats, except for plasma adiponectin, four to six rats, and mRNA expression, four to five rats from each group. In other words, the values/groups bearing common alphabets/superscripts are not statistically different.…”

Section: Discussionmentioning

confidence: 99%

“…This is quite intriguing, because C/EBP is required for adipocyte differentiation, as it triggers the PPARγ expression, which is an essential transcription factor of adipogenic differentiation process. 35,36 Thus, it appears that the protein status of these transcriptional factors, rather mRNA levels, may possibly explain the adipocyte differentiation. Nevertheless, it is evident that the observed elevation of ZFP423 mRNA is suggestive of increased preadipocyte differentiation to house triglyceride, arising out of excess fructose ingestion and thus resulting in adipocyte hypertrophy of RPWAT.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A and its metabolic pathway play a determinant role in high‐fructose‐induced triglyceride accumulation of the visceral adipose depot of male Wistar rats

Reddy

Mahesh

Munikumar

et al. 2019

Cell Biochemistry & Function

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Here, we tested a hypothesis that vitamin A and/or its metabolic pathways are involved in the high-fructose-mediated alteration in adipose tissue biology. For this purpose, weanling male Wistar rats were provided with one of the following diets: control (C), control with vitamin A deficiency (C-VAD), high fructose (HFr), and HFr with VAD (HFr-VAD) for 16 weeks, except that half of the C-VAD diet-fed rats were shifted to HFr diet (C-VAD(s)HFr), after 8-week period. Compared with control, feeding of HFr diet significantly increased the triglyceride content (P ≤ .01) and thus adipocyte size (hypertrophy) (P ≤ .001) in visceral adipose depot; retroperitoneal white adipose tissue (RPWAT) and these changes were corroborated with de novo lipogenesis, as evidenced by the increased glycerol-3-phosphate dehydrogenase activity (P ≤ .01) and up-regulation of lipogenic pathway transcripts, fructose transporter, and aldehyde dehydrogenase 1 A1. On the contrary, the absence of vitamin A in the HFr diet (HFr-VAD) failed to exert these changes; however, it induced adipocyte hyperplasia. Further, vitamin A deficiency-mediated changes were reversed by replenishment, as evident from the group that was shifted from C-VAD to HFr diet.In conclusion, vitamin A and its metabolic pathway play a key determinant role in the high-fructose-induced triglyceride accumulation and adipocyte hypertrophy of visceral white adipose depot.Significance of the study: Here, we report the metabolic impact of high-fructose feeding under vitamin A-sufficient and vitamin A-deficient conditions. Feeding of high-fructose diet induced triglyceride accumulation and adipocyte hypertrophy of the visceral white adipose depots. These changes corroborated with augmented expression of vitamin A and lipid metabolic pathway genes. Contrarily, absence of vitamin A in the high-fructose diet did not elicit such responses, while vitamin A

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“…PPARγ is both sufficient and necessary for conversion of preadipocytes into adipocytes and is a master regulator of adipogenesis (6). …”

Section: Introductionmentioning

confidence: 99%

In Vitro Differentiation of Preosteoblast-Like Cells, MC3T3-E1, to Adipocytes Is Enhanced by 1,25(OH)2 Vitamin D3

Pendleton

Chandar

2017

Front. Endocrinol.

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Osteoblasts and adipocytes originate from common mesenchymal progenitor cells and are controlled by specific transcription factors. While 1,25-dihydroxyvitamin D3 (vitamin D) is known to be an important factor for osteoblast differentiation, there are conflicting reports regarding its effect on adipogenesis. In this study, we attempted to understand the effect of exposure of preosteoblasts (MC3T3-E1) to adipogenic media with and without vitamin D and determined the expression of adipogenic genes during this process. Our studies show that while transdifferentiation of preosteoblasts occurred on exposure to adipogenic media, the effect of vitamin D treatment was synergistic resulting in several hundred fold increase in adipocyte transcription factors C/EBPα and peroxisome proliferator-activated receptor-gamma (P < 0.001) along with an increase in markers of adipogenesis and accumulation of lipid droplets in cells. Vitamin D treatment was also accompanied by 100-fold to 700-fold increases in vitamin D receptor expression during the treatment period (P < 0.001). To determine how the effect of vitamin D might compare to other genetic manipulations that promote adipogenic differentiation, we stably knocked down retinoblastoma expression in MC3T3-E1 cells. Recent studies have suggested retinoblastoma (Rb1) tumor suppressor gene function to be critical to maintain osteoblasts function and inhibit adipocyte differentiation. We exposed MC3T3-E1 cells with reduced Rb1 expression to adipogenic media and found an increase in adipogenic differentiation when compared to cells with a full complement of Rb dosage. However, the extent of the change was not as dramatic as seen with vitamin D. These studies show that preosteoblasts are sensitive and respond to these manipulations that favor the adipocytic phenotype. While vitamin D is not known to directly affect targets in adipogenesis, our observations may have resulted from the malleability of preosteoblast genome in MC3T3-E1 cells, which allowed adipocyte specific gene expression under appropriate stimuli. Why this pathway is influenced and subverted by an anabolic bone factor such as vitamin D remains to be determined.

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The increasingly complex regulation of adipocyte differentiation

Cited by 40 publications

References 82 publications

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Vitamin A and its metabolic pathway play a determinant role in high‐fructose‐induced triglyceride accumulation of the visceral adipose depot of male Wistar rats

In Vitro Differentiation of Preosteoblast-Like Cells, MC3T3-E1, to Adipocytes Is Enhanced by 1,25(OH)2 Vitamin D3

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