Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure.
Recent evidence has suggested that AHNAK expression is altered in obesity, although its role in adipose tissue development remains unclear. The objective of this study was to determine the molecular mechanism by which Ahnak influences adipogenesis and glucose homeostasis.We investigated the in vitro...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4605776?pdf=render |
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| author | Jae Hoon Shin Il Yong Kim Yo Na Kim Sun Mee Shin Kyung Jin Roh Seo Hyun Lee Mira Sohn Soo Young Cho Sang Hyuk Lee Chang-Yong Ko Han-Sung Kim Cheol Soo Choi Yun Soo Bae Je Kyung Seong |
| author_facet | Jae Hoon Shin Il Yong Kim Yo Na Kim Sun Mee Shin Kyung Jin Roh Seo Hyun Lee Mira Sohn Soo Young Cho Sang Hyuk Lee Chang-Yong Ko Han-Sung Kim Cheol Soo Choi Yun Soo Bae Je Kyung Seong |
| author_sort | Jae Hoon Shin |
| collection | DOAJ |
| description | Recent evidence has suggested that AHNAK expression is altered in obesity, although its role in adipose tissue development remains unclear. The objective of this study was to determine the molecular mechanism by which Ahnak influences adipogenesis and glucose homeostasis.We investigated the in vitro role of AHNAK in adipogenesis using adipose-derived mesenchymal stem cells (ADSCs) and C3H10T1/2 cells. AHNAK-KO male mice were fed a high-fat diet (HFD; 60% calories from fat) and examined for glucose and insulin tolerances, for body fat compositions, and by hyperinsulinemic-euglycemic clamping. Energy expenditures were assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in white or brown adipose tissues.Adipogenesis in ADSCs was impaired in AHNAK-KO mice. The loss of AHNAK led to decreased BMP4/SMAD1 signaling, resulting in the downregulation of key regulators of adipocyte differentiation (P<0.05). AHNAK directly interacted with SMAD1 on the Pparγ2 promoter. Concomitantly, HFD-fed AHNAK-KO mice displayed reduced hepatosteatosis and improved metabolic profiles, including improved glucose tolerance (P<0.001), enhanced insulin sensitivity (P<0.001), and increased energy expenditure (P<0.05), without undergoing alterations in food intake and physical activity.AHNAK plays a crucial role in body fat accumulation by regulating adipose tissue development via interaction with the SMAD1 protein and can be involved in metabolic homeostasis. |
| first_indexed | 2024-12-10T21:52:44Z |
| format | Article |
| id | doaj.art-634ddadeb6e041c1a978485d20182ff3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T21:52:44Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-634ddadeb6e041c1a978485d20182ff32022-12-22T01:32:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013972010.1371/journal.pone.0139720Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure.Jae Hoon ShinIl Yong KimYo Na KimSun Mee ShinKyung Jin RohSeo Hyun LeeMira SohnSoo Young ChoSang Hyuk LeeChang-Yong KoHan-Sung KimCheol Soo ChoiYun Soo BaeJe Kyung SeongRecent evidence has suggested that AHNAK expression is altered in obesity, although its role in adipose tissue development remains unclear. The objective of this study was to determine the molecular mechanism by which Ahnak influences adipogenesis and glucose homeostasis.We investigated the in vitro role of AHNAK in adipogenesis using adipose-derived mesenchymal stem cells (ADSCs) and C3H10T1/2 cells. AHNAK-KO male mice were fed a high-fat diet (HFD; 60% calories from fat) and examined for glucose and insulin tolerances, for body fat compositions, and by hyperinsulinemic-euglycemic clamping. Energy expenditures were assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in white or brown adipose tissues.Adipogenesis in ADSCs was impaired in AHNAK-KO mice. The loss of AHNAK led to decreased BMP4/SMAD1 signaling, resulting in the downregulation of key regulators of adipocyte differentiation (P<0.05). AHNAK directly interacted with SMAD1 on the Pparγ2 promoter. Concomitantly, HFD-fed AHNAK-KO mice displayed reduced hepatosteatosis and improved metabolic profiles, including improved glucose tolerance (P<0.001), enhanced insulin sensitivity (P<0.001), and increased energy expenditure (P<0.05), without undergoing alterations in food intake and physical activity.AHNAK plays a crucial role in body fat accumulation by regulating adipose tissue development via interaction with the SMAD1 protein and can be involved in metabolic homeostasis.http://europepmc.org/articles/PMC4605776?pdf=render |
| spellingShingle | Jae Hoon Shin Il Yong Kim Yo Na Kim Sun Mee Shin Kyung Jin Roh Seo Hyun Lee Mira Sohn Soo Young Cho Sang Hyuk Lee Chang-Yong Ko Han-Sung Kim Cheol Soo Choi Yun Soo Bae Je Kyung Seong Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. PLoS ONE |
| title | Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. |
| title_full | Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. |
| title_fullStr | Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. |
| title_full_unstemmed | Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. |
| title_short | Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. |
| title_sort | obesity resistance and enhanced insulin sensitivity in ahnak mice fed a high fat diet are related to impaired adipogenesis and increased energy expenditure |
| url | http://europepmc.org/articles/PMC4605776?pdf=render |
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