Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring
Abstract Background: Maternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysf...
| Autores principales: | , , , , , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | inglés |
| Publicado: |
BioMed Central
2018
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| Materias: | |
| Acceso en línea: | http://eprints.uanl.mx/16206/1/120.pdf |
| _version_ | 1824414534147768320 |
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| author | Cárdenas Pérez, Robbi Elizabeth Fuentes Mera, Lizeth De la Garza, Ana Laura Torre Villalvazo, Iván Reyes Castro, Luis A. Rodríguez Rocha, Humberto García García, Aracely Corona Castillo, Juan Carlos Tovar, Armando R. Zambrano, Elena Ortiz López, Rocío Saville, Jennifer Fuller, Maria Camacho Morales, Alberto |
| author_facet | Cárdenas Pérez, Robbi Elizabeth Fuentes Mera, Lizeth De la Garza, Ana Laura Torre Villalvazo, Iván Reyes Castro, Luis A. Rodríguez Rocha, Humberto García García, Aracely Corona Castillo, Juan Carlos Tovar, Armando R. Zambrano, Elena Ortiz López, Rocío Saville, Jennifer Fuller, Maria Camacho Morales, Alberto |
| author_sort | Cárdenas Pérez, Robbi Elizabeth |
| collection | Repositorio Institucional |
| description | Abstract Background: Maternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysfunction. Using three selective diet formula including a High fat diet (HFD), Cafeteria (CAF) and High Sugar Diet (HSD), we hypothesized that maternal diets exposure program leads to selective changes in hypothalamic mitochondria fusion and fission dynamics in male offspring leading to metabolic dysfunction which is exacerbated by a second exposure after weaning. Methods: We exposed female Wistar rats to nutritional programming including Chow, HFD, CAF, or HSD for 9 weeks (pre-mating, mating, pregnancy and lactation) or to the same diets to offspring after weaning. We determined body weight, food intake and metabolic parameters in the offspring from 21 to 60 days old. Hypothalamus was dissected at 60 days old to determine mitochondria-ER interaction markers by mRNA expression and western blot and morphology by transmission electron microscopy (TEM). Mitochondrial-ER function was analyzed by confocal microscopy using hypothalamic cell line mHypoA-CLU192. Results: Maternal programming by HFD and CAF leads to failure in glucose, leptin and insulin sensitivity and fat accumulation. Additionally, HFD and CAF programming promote mitochondrial fusion by increasing the expression of MFN2 and decreasing DRP1, respectively. Further, TEM analysis confirms that CAF exposure after programing leads to an increase in mitochondria fusion and enhanced mitochondrial-ER interaction, which partially correlates with metabolic dysfunction and fat accumulation in the HFD and CAF groups. Finally, we identified that lipotoxic palmitic acid stimulus in hypothalamic cells increases Ca2+ overload into mitochondria matrix leading to mitochondrial dysfunction. Conclusions: We concluded that maternal programming by HFD induces hypothalamic mitochondria fusion, metabolic dysfunction and fat accumulation in male offspring, which is exacerbated by HFD or CAF exposure after weaning, potentially due to mitochondria calcium overflux. |
| format | Article |
| id | eprints-16206 |
| institution | UANL |
| language | English |
| publishDate | 2018 |
| publisher | BioMed Central |
| record_format | eprints |
| spelling | eprints-162062024-03-04T15:46:38Z http://eprints.uanl.mx/16206/ Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring Cárdenas Pérez, Robbi Elizabeth Fuentes Mera, Lizeth De la Garza, Ana Laura Torre Villalvazo, Iván Reyes Castro, Luis A. Rodríguez Rocha, Humberto García García, Aracely Corona Castillo, Juan Carlos Tovar, Armando R. Zambrano, Elena Ortiz López, Rocío Saville, Jennifer Fuller, Maria Camacho Morales, Alberto QP Fisiología Abstract Background: Maternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysfunction. Using three selective diet formula including a High fat diet (HFD), Cafeteria (CAF) and High Sugar Diet (HSD), we hypothesized that maternal diets exposure program leads to selective changes in hypothalamic mitochondria fusion and fission dynamics in male offspring leading to metabolic dysfunction which is exacerbated by a second exposure after weaning. Methods: We exposed female Wistar rats to nutritional programming including Chow, HFD, CAF, or HSD for 9 weeks (pre-mating, mating, pregnancy and lactation) or to the same diets to offspring after weaning. We determined body weight, food intake and metabolic parameters in the offspring from 21 to 60 days old. Hypothalamus was dissected at 60 days old to determine mitochondria-ER interaction markers by mRNA expression and western blot and morphology by transmission electron microscopy (TEM). Mitochondrial-ER function was analyzed by confocal microscopy using hypothalamic cell line mHypoA-CLU192. Results: Maternal programming by HFD and CAF leads to failure in glucose, leptin and insulin sensitivity and fat accumulation. Additionally, HFD and CAF programming promote mitochondrial fusion by increasing the expression of MFN2 and decreasing DRP1, respectively. Further, TEM analysis confirms that CAF exposure after programing leads to an increase in mitochondria fusion and enhanced mitochondrial-ER interaction, which partially correlates with metabolic dysfunction and fat accumulation in the HFD and CAF groups. Finally, we identified that lipotoxic palmitic acid stimulus in hypothalamic cells increases Ca2+ overload into mitochondria matrix leading to mitochondrial dysfunction. Conclusions: We concluded that maternal programming by HFD induces hypothalamic mitochondria fusion, metabolic dysfunction and fat accumulation in male offspring, which is exacerbated by HFD or CAF exposure after weaning, potentially due to mitochondria calcium overflux. BioMed Central 2018 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/16206/1/120.pdf http://eprints.uanl.mx/16206/1.haspreviewThumbnailVersion/120.pdf Cárdenas Pérez, Robbi Elizabeth y Fuentes Mera, Lizeth y De la Garza, Ana Laura y Torre Villalvazo, Iván y Reyes Castro, Luis A. y Rodríguez Rocha, Humberto y García García, Aracely y Corona Castillo, Juan Carlos y Tovar, Armando R. y Zambrano, Elena y Ortiz López, Rocío y Saville, Jennifer y Fuller, Maria y Camacho Morales, Alberto (2018) Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring. Nutrition & Metabolism, 15 (1). pp. 1-16. ISSN 1743-7075 http://doi.org/10.1186/s12986-018-0279-6 doi:10.1186/s12986-018-0279-6 |
| spellingShingle | QP Fisiología Cárdenas Pérez, Robbi Elizabeth Fuentes Mera, Lizeth De la Garza, Ana Laura Torre Villalvazo, Iván Reyes Castro, Luis A. Rodríguez Rocha, Humberto García García, Aracely Corona Castillo, Juan Carlos Tovar, Armando R. Zambrano, Elena Ortiz López, Rocío Saville, Jennifer Fuller, Maria Camacho Morales, Alberto Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| title_full | Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| title_fullStr | Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| title_full_unstemmed | Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| title_short | Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| title_sort | maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring |
| topic | QP Fisiología |
| url | http://eprints.uanl.mx/16206/1/120.pdf |
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