Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis
Summary: Both humans and mice with congenital generalized lipodystrophy due to AGPAT2 deficiency develop diabetes mellitus, insulin resistance, and hepatic steatosis, which have been attributed to the near total loss of adipose tissue (AT). Here, we show that regulated AT regeneration in doxycycline...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224007387 |
| _version_ | 1827287372355600384 |
|---|---|
| author | Anil K. Agarwal Katie Tunison Jay D. Horton Abhimanyu Garg |
| author_facet | Anil K. Agarwal Katie Tunison Jay D. Horton Abhimanyu Garg |
| author_sort | Anil K. Agarwal |
| collection | DOAJ |
| description | Summary: Both humans and mice with congenital generalized lipodystrophy due to AGPAT2 deficiency develop diabetes mellitus, insulin resistance, and hepatic steatosis, which have been attributed to the near total loss of adipose tissue (AT). Here, we show that regulated AT regeneration in doxycycline (dox)-fed Tg−AT-hAGPAT2;mAgpat2−/− mice partially ameliorates hepatic steatosis at 12 weeks of age and causes reduced expression of genes involved in hepatic de novo lipogenesis despite partial (∼30–50%) AT regeneration compared to that in wild-type mice. Compared to chow-fed Tg−AT-hAGPAT2;mAgpat2−/− mice, those fed dox diet had markedly reduced serum insulin levels, suggesting an improvement in insulin resistance. Interestingly, the fasting plasma glucose levels in dox-fed Tg−AT-hAGPAT2;mAgpat2−/− mice were no different than those in chow-fed wild-type mice. Indirect calorimetry revealed normalization in the energy balance of dox-fed Tg−AT-hAGPAT2;mAgpat2−/− mice compared to that in chow-fed mice. This study’s findings suggest that partial AT regeneration in lipodystrophic mice can ameliorate metabolic derangements. |
| first_indexed | 2024-04-24T10:57:15Z |
| format | Article |
| id | doaj.art-3b46cd7f3a354f9a9e35118f7af216af |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T10:57:15Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3b46cd7f3a354f9a9e35118f7af216af2024-04-12T04:45:40ZengElsevieriScience2589-00422024-04-01274109517Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosisAnil K. Agarwal0Katie Tunison1Jay D. Horton2Abhimanyu Garg3Section of Nutrition and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding authorSection of Nutrition and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390, USACenter for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390, USASection of Nutrition and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390, USASummary: Both humans and mice with congenital generalized lipodystrophy due to AGPAT2 deficiency develop diabetes mellitus, insulin resistance, and hepatic steatosis, which have been attributed to the near total loss of adipose tissue (AT). Here, we show that regulated AT regeneration in doxycycline (dox)-fed Tg−AT-hAGPAT2;mAgpat2−/− mice partially ameliorates hepatic steatosis at 12 weeks of age and causes reduced expression of genes involved in hepatic de novo lipogenesis despite partial (∼30–50%) AT regeneration compared to that in wild-type mice. Compared to chow-fed Tg−AT-hAGPAT2;mAgpat2−/− mice, those fed dox diet had markedly reduced serum insulin levels, suggesting an improvement in insulin resistance. Interestingly, the fasting plasma glucose levels in dox-fed Tg−AT-hAGPAT2;mAgpat2−/− mice were no different than those in chow-fed wild-type mice. Indirect calorimetry revealed normalization in the energy balance of dox-fed Tg−AT-hAGPAT2;mAgpat2−/− mice compared to that in chow-fed mice. This study’s findings suggest that partial AT regeneration in lipodystrophic mice can ameliorate metabolic derangements.http://www.sciencedirect.com/science/article/pii/S2589004224007387LipidPathophysiologyPhysiology |
| spellingShingle | Anil K. Agarwal Katie Tunison Jay D. Horton Abhimanyu Garg Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis iScience Lipid Pathophysiology Physiology |
| title | Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis |
| title_full | Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis |
| title_fullStr | Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis |
| title_full_unstemmed | Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis |
| title_short | Regulated regeneration of adipose tissue in lipodystrophic Agpat2-null mice partially ameliorates hepatic steatosis |
| title_sort | regulated regeneration of adipose tissue in lipodystrophic agpat2 null mice partially ameliorates hepatic steatosis |
| topic | Lipid Pathophysiology Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224007387 |
| work_keys_str_mv | AT anilkagarwal regulatedregenerationofadiposetissueinlipodystrophicagpat2nullmicepartiallyameliorateshepaticsteatosis AT katietunison regulatedregenerationofadiposetissueinlipodystrophicagpat2nullmicepartiallyameliorateshepaticsteatosis AT jaydhorton regulatedregenerationofadiposetissueinlipodystrophicagpat2nullmicepartiallyameliorateshepaticsteatosis AT abhimanyugarg regulatedregenerationofadiposetissueinlipodystrophicagpat2nullmicepartiallyameliorateshepaticsteatosis |