Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content
Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.718962/full |
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| author | Natalie Burchat Priyanka Sharma Hong Ye Sai Santosh Babu Komakula Sai Santosh Babu Komakula Agnieszka Dobrzyn Agnieszka Dobrzyn Vladimir Vartanian R. Stephen Lloyd R. Stephen Lloyd Harini Sampath Harini Sampath Harini Sampath |
| author_facet | Natalie Burchat Priyanka Sharma Hong Ye Sai Santosh Babu Komakula Sai Santosh Babu Komakula Agnieszka Dobrzyn Agnieszka Dobrzyn Vladimir Vartanian R. Stephen Lloyd R. Stephen Lloyd Harini Sampath Harini Sampath Harini Sampath |
| author_sort | Natalie Burchat |
| collection | DOAJ |
| description | Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese (Ay/a) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in Ay/a mice (Ay/aTg) prevents increased body weight, without reducing food intake. Instead, obesity resistance in Ay/aTg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the Ay/a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring. |
| first_indexed | 2024-12-16T22:13:50Z |
| format | Article |
| id | doaj.art-b85df084bf71476c84f748558a8a9977 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T22:13:50Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b85df084bf71476c84f748558a8a99772022-12-21T22:14:14ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.718962718962Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial ContentNatalie Burchat0Priyanka Sharma1Hong Ye2Sai Santosh Babu Komakula3Sai Santosh Babu Komakula4Agnieszka Dobrzyn5Agnieszka Dobrzyn6Vladimir Vartanian7R. Stephen Lloyd8R. Stephen Lloyd9Harini Sampath10Harini Sampath11Harini Sampath12Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesRutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesRutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesRutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesLaboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, PolandRutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesLaboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, PolandOregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United StatesOregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United StatesDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, United StatesRutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesDepartment of Nutritional Sciences, Rutgers University, New Brunswick, NJ, United StatesCenter for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United StatesObesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese (Ay/a) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in Ay/a mice (Ay/aTg) prevents increased body weight, without reducing food intake. Instead, obesity resistance in Ay/aTg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the Ay/a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring.https://www.frontiersin.org/articles/10.3389/fcell.2021.718962/fullDNA repairmetabolic syndrome (in offspring)obesitydevelopmental origins of diseasemitochondrial function |
| spellingShingle | Natalie Burchat Priyanka Sharma Hong Ye Sai Santosh Babu Komakula Sai Santosh Babu Komakula Agnieszka Dobrzyn Agnieszka Dobrzyn Vladimir Vartanian R. Stephen Lloyd R. Stephen Lloyd Harini Sampath Harini Sampath Harini Sampath Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content Frontiers in Cell and Developmental Biology DNA repair metabolic syndrome (in offspring) obesity developmental origins of disease mitochondrial function |
| title | Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content |
| title_full | Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content |
| title_fullStr | Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content |
| title_full_unstemmed | Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content |
| title_short | Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content |
| title_sort | maternal transmission of human ogg1 protects mice against genetically and diet induced obesity through increased tissue mitochondrial content |
| topic | DNA repair metabolic syndrome (in offspring) obesity developmental origins of disease mitochondrial function |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.718962/full |
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