Dynamics of HOX gene expression and regulation in adipocyte development

Kumar, Vinod; Sekar, Mouliganesh; Sarkar, Priyanka; Acharya, Kshitish K.; Thirumurugan, Kavitha

doi:10.1016/j.gene.2020.145308

Cited by 13 publications

(7 citation statements)

References 39 publications

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“…We found that several genes from the homeobox (HOX) family of proteins were uniquely expressed in metacarpal adipose tissue. These genes are known to play important roles in the differentiation of adipocytes [50]. Furthermore, several genes associated with cytokines and immune response appeared to be downregulated in the metacarpal tissue during spring (S5 and S8 Table ).…”

Section: Discussionmentioning

confidence: 98%

Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

Weldenegodguad

Pokharel

Niiranen

et al. 2021

Preprint

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Reindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging arctic conditions of northern Eurasia. Adipose tissues play a crucial role in animals living in northern environments by altering gene expression in their tissues to regulate energy homeostasis and thermogenic activity. Here, we performed transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during two seasonal time points (spring and winter). On average 36.5 million pair-ended clean reads were obtained for each sample, and a total of 16,362 genes were expressed in our data. Gene expression profiles in metacarpal tissue were distinct and clustered separately from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appeared to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, when the animals are in less optimal condition, genes associated with the immune system (e.g., CCL2, CCL11, CXCL14, IGSF3, IGHM, IGLC7, IGKC, JCHAIN, and IGSF10) were upregulated in the perirenal and prescapular adipose tissue, while genes involved in energy metabolism (e.g., ACOT2, APOA1, ANGPTL1, ANGPTL8, ELOVL7, MSMO1, PFKFB1, and ST3GAL6) were upregulated in metacarpal tissue. Even reindeer harboured relatively fewer significantly differentially expressed genes than Finnish reindeer, irrespective of the season, possibly owing to climatic and management differences. Moreover, blood and tissue parameters reflecting general physiological and metabolic status showed less seasonal variation in Even reindeer than in Finnish reindeer. This study identified adipose candidate genes potentially involved in immune response, fat deposition, energy metabolism, development, cell growth, and organogenesis. Taken together, this study provides new information on the mechanisms by which reindeer adapt to less optimal arctic conditions.

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Section: Discussionmentioning

confidence: 98%

Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

Weldenegodguad

Pokharel

Niiranen

et al. 2021

Preprint

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“…In the present report, we have described a previously unrecognized role of the HOXA5 transcription factor in regulating human adipogenesis. Previous studies have shown that in humans, HOXA5 is highly expressed in different adipose tissue depots, and plays an active role in controlling both adipocyte function and body fat distribution [ 6 , 28 ]. In addition, we previously reported that Hoxa5 silencing impaired adipocyte differentiation in mouse 3T3-L1 preadipocytes [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Dysregulation of the Homeobox A5 (HOXA5) Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity

Parrillo

Spinelli

Costanzo

et al. 2022

Cells

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Along with insulin resistance and increased risk of type 2 diabetes (T2D), lean first-degree relatives of T2D subjects (FDR) feature impaired adipogenesis in subcutaneous adipose tissue (SAT) and subcutaneous adipocyte hypertrophy well before diabetes onset. The molecular mechanisms linking these events have only partially been clarified. In the present report, we show that silencing of the transcription factor Homeobox A5 (HOXA5) in human preadipocytes impaired differentiation in mature adipose cells in vitro. The reduced adipogenesis was accompanied by inappropriate WNT-signaling activation. Importantly, in preadipocytes from FDR individuals, HOXA5 expression was attenuated, with hypermethylation of the HOXA5 promoter region found responsible for its downregulation, as revealed by luciferase assay. Both HOXA5 gene expression and DNA methylation were significantly correlated with SAT adipose cell hypertrophy in FDR, whose increased adipocyte size marks impaired adipogenesis. In preadipocytes from FDR, the low HOXA5 expression negatively correlated with enhanced transcription of the WNT signaling downstream genes NFATC1 and WNT2B. In silico evidence indicated that NFATC1 and WNT2B were directly controlled by HOXA5. The HOXA5 promoter region also was hypermethylated in peripheral blood leukocytes from these same FDR individuals, which was further revealed in peripheral blood leukocytes from an independent group of obese subjects. Thus, HOXA5 controlled adipogenesis in humans by suppressing WNT signaling. Altered DNA methylation of the HOXA5 promoter contributed to restricted adipogenesis in the SAT of lean subjects who were FDR of type 2 diabetics and in obese individuals.

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“…We found that several genes from the homeobox (HOX) family of proteins were uniquely expressed in metacarpal adipose tissue. These genes are known to play important roles in the differentiation of adipocytes 50 . Furthermore, several genes associated with cytokines and immune response appeared to be downregulated in the metacarpal tissue during spring (Supplementary Data S6 and S10).…”

Section: Discussionmentioning

confidence: 99%

Adipose gene expression profiles reveal insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

et al. 2021

View full text Add to dashboard Cite

Reindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging conditions of northern Eurasia. Adipose tissues play a crucial role in northern animals by altering gene expression in their tissues to regulate energy homoeostasis and thermogenic activity. Here, we perform transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during spring and winter. A total of 16,212 genes are expressed in our data. Gene expression profiles in metacarpal tissue are distinct from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appears to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, genes associated with the immune system are upregulated in the perirenal and prescapular adipose tissue. Blood and tissue parameters reflecting general physiological and metabolic status show less seasonal variation in Even reindeer than in Finnish reindeer. This study identifies candidate genes potentially involved in immune response, fat deposition, and energy metabolism and provides new information on the mechanisms by which reindeer adapt to harsh arctic conditions.

show abstract

Dynamics of HOX gene expression and regulation in adipocyte development

Cited by 13 publications

References 39 publications

Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

Epigenetic Dysregulation of the Homeobox A5 (HOXA5) Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity

Adipose gene expression profiles reveal insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

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