Cargando…
Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes
BACKGROUND: Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)–peroxisome prolif...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Diabetes Association
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244199/ https://www.ncbi.nlm.nih.gov/pubmed/36872063 http://dx.doi.org/10.4093/dmj.2022.0156 |
_version_ | 1785054584762269696 |
---|---|
author | Kim, Praise Chanmee Lee, Ji Seon Chung, Sung Soo Park, Kyong Soo |
author_facet | Kim, Praise Chanmee Lee, Ji Seon Chung, Sung Soo Park, Kyong Soo |
author_sort | Kim, Praise Chanmee |
collection | PubMed |
description | BACKGROUND: Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)–peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown. Here, we investigated the role of SENP2 in the regulation of fatty acid metabolism by leptin in adipocytes and white adipose tissues. METHODS: The effects of leptin mediated by SENP2 on fatty acid metabolism were tested by siRNA-mediated knockdown in 3T3-L1 adipocytes. The role of SENP2 was confirmed in vivo using adipocyte-specific Senp2 knockout (Senp2-aKO) mice. We revealed the molecular mechanism involved in the leptin-induced transcriptional regulation of carnitine palmitoyl transferase 1b (Cpt1b) and long-chain acyl-coenzyme A synthetase 1 (Acsl1) using transfection/reporter assays and chromatin immunoprecipitation. RESULTS: SENP2 mediated the increased expression of FAO-associated enzymes, CPT1b and ACSL1, which peaked 24 hours after leptin treatment in adipocytes. In contrast, leptin stimulated FAO through AMPK during the initial several hours after treatment. In white adipose tissues, FAO and mRNA levels of Cpt1b and Acsl1 were increased by 2-fold 24 hours after leptin injection in control mice but not in Senp2-aKO mice. Leptin increased PPARα binding to the Cpt1b and Acsl1 promoters in adipocytes through SENP2. CONCLUSION: These results suggest that the SENP2-PPARα pathway plays an important role in leptin-induced FAO in white adipocytes. |
format | Online Article Text |
id | pubmed-10244199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Korean Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-102441992023-06-08 Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes Kim, Praise Chanmee Lee, Ji Seon Chung, Sung Soo Park, Kyong Soo Diabetes Metab J Original Article BACKGROUND: Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)–peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown. Here, we investigated the role of SENP2 in the regulation of fatty acid metabolism by leptin in adipocytes and white adipose tissues. METHODS: The effects of leptin mediated by SENP2 on fatty acid metabolism were tested by siRNA-mediated knockdown in 3T3-L1 adipocytes. The role of SENP2 was confirmed in vivo using adipocyte-specific Senp2 knockout (Senp2-aKO) mice. We revealed the molecular mechanism involved in the leptin-induced transcriptional regulation of carnitine palmitoyl transferase 1b (Cpt1b) and long-chain acyl-coenzyme A synthetase 1 (Acsl1) using transfection/reporter assays and chromatin immunoprecipitation. RESULTS: SENP2 mediated the increased expression of FAO-associated enzymes, CPT1b and ACSL1, which peaked 24 hours after leptin treatment in adipocytes. In contrast, leptin stimulated FAO through AMPK during the initial several hours after treatment. In white adipose tissues, FAO and mRNA levels of Cpt1b and Acsl1 were increased by 2-fold 24 hours after leptin injection in control mice but not in Senp2-aKO mice. Leptin increased PPARα binding to the Cpt1b and Acsl1 promoters in adipocytes through SENP2. CONCLUSION: These results suggest that the SENP2-PPARα pathway plays an important role in leptin-induced FAO in white adipocytes. Korean Diabetes Association 2023-05 2023-03-06 /pmc/articles/PMC10244199/ /pubmed/36872063 http://dx.doi.org/10.4093/dmj.2022.0156 Text en Copyright © 2023 Korean Diabetes Association https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Praise Chanmee Lee, Ji Seon Chung, Sung Soo Park, Kyong Soo Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes |
title | Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes |
title_full | Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes |
title_fullStr | Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes |
title_full_unstemmed | Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes |
title_short | Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes |
title_sort | role of sumo-specific protease 2 in leptin-induced fatty acid metabolism in white adipocytes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244199/ https://www.ncbi.nlm.nih.gov/pubmed/36872063 http://dx.doi.org/10.4093/dmj.2022.0156 |
work_keys_str_mv | AT kimpraisechanmee roleofsumospecificprotease2inleptininducedfattyacidmetabolisminwhiteadipocytes AT leejiseon roleofsumospecificprotease2inleptininducedfattyacidmetabolisminwhiteadipocytes AT chungsungsoo roleofsumospecificprotease2inleptininducedfattyacidmetabolisminwhiteadipocytes AT parkkyongsoo roleofsumospecificprotease2inleptininducedfattyacidmetabolisminwhiteadipocytes |