Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK
Maternal high-fat (HF) is associated with offspring hyperphagia and obesity. We hypothesized that maternal HF alters fetal neuroprogenitor cell (NPC) and hypothalamic arcuate nucleus (ARC) development with preferential differentiation of neurons towards orexigenic (NPY/AgRP) versus anorexigenic (POM...
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MDPI AG
2020-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/11/3326 |
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| author | Mina Desai Monica G. Ferrini Guang Han Kavita Narwani Michael G. Ross |
| author_facet | Mina Desai Monica G. Ferrini Guang Han Kavita Narwani Michael G. Ross |
| author_sort | Mina Desai |
| collection | DOAJ |
| description | Maternal high-fat (HF) is associated with offspring hyperphagia and obesity. We hypothesized that maternal HF alters fetal neuroprogenitor cell (NPC) and hypothalamic arcuate nucleus (ARC) development with preferential differentiation of neurons towards orexigenic (NPY/AgRP) versus anorexigenic (POMC) neurons, leading to offspring hyperphagia and obesity. Furthermore, these changes may involve hypothalamic bHLH neuroregulatory factors (Hes1, Mash1, Ngn3) and energy sensor AMPK. Female mice were fed either a control or a high fat (HF) diet prior to mating, and during pregnancy and lactation. HF male newborns were heavier at birth and exhibited decreased protein expression of hypothalamic bHLH factors, pAMPK/AMPK and POMC with increased AgRP. As adults, these changes persisted though with increased ARC pAMPK/AMPK. Importantly, the total NPY neurons were increased, which was consistent with the increased food intake and adult fat mass. Further, NPCs from HF newborn hypothalamic tissue showed similar changes with preferential NPC neuronal differentiation towards NPY. Lastly, the role of AMPK was further confirmed with in vitro treatment of Control NPCs with pharmacologic AMPK modulators. Thus, the altered ARC development of HF offspring results in excess appetite and reduced satiety leading to obesity. The underlying mechanism may involve AMPK/bHLH pathways. |
| first_indexed | 2024-03-10T15:14:52Z |
| format | Article |
| id | doaj.art-70c7100ed064480b893d8cc9b078138a |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T15:14:52Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-70c7100ed064480b893d8cc9b078138a2023-11-20T19:00:49ZengMDPI AGNutrients2072-66432020-10-011211332610.3390/nu12113326Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPKMina Desai0Monica G. Ferrini1Guang Han2Kavita Narwani3Michael G. Ross4Department of Obstetrics and Gynecology, Perinatal Research Laboratory, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADepartment of Health and Life Sciences, Charles R. Drew University, Los Angeles, CA 90059, USADepartment of Obstetrics and Gynecology, Perinatal Research Laboratory, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADepartment of Obstetrics and Gynecology, Perinatal Research Laboratory, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADepartment of Obstetrics and Gynecology, Perinatal Research Laboratory, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USAMaternal high-fat (HF) is associated with offspring hyperphagia and obesity. We hypothesized that maternal HF alters fetal neuroprogenitor cell (NPC) and hypothalamic arcuate nucleus (ARC) development with preferential differentiation of neurons towards orexigenic (NPY/AgRP) versus anorexigenic (POMC) neurons, leading to offspring hyperphagia and obesity. Furthermore, these changes may involve hypothalamic bHLH neuroregulatory factors (Hes1, Mash1, Ngn3) and energy sensor AMPK. Female mice were fed either a control or a high fat (HF) diet prior to mating, and during pregnancy and lactation. HF male newborns were heavier at birth and exhibited decreased protein expression of hypothalamic bHLH factors, pAMPK/AMPK and POMC with increased AgRP. As adults, these changes persisted though with increased ARC pAMPK/AMPK. Importantly, the total NPY neurons were increased, which was consistent with the increased food intake and adult fat mass. Further, NPCs from HF newborn hypothalamic tissue showed similar changes with preferential NPC neuronal differentiation towards NPY. Lastly, the role of AMPK was further confirmed with in vitro treatment of Control NPCs with pharmacologic AMPK modulators. Thus, the altered ARC development of HF offspring results in excess appetite and reduced satiety leading to obesity. The underlying mechanism may involve AMPK/bHLH pathways.https://www.mdpi.com/2072-6643/12/11/3326developmental programmingneuropeptideshypothalamic arcuate nucleusneuroprogenitor cellsAMPK activator |
| spellingShingle | Mina Desai Monica G. Ferrini Guang Han Kavita Narwani Michael G. Ross Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK Nutrients developmental programming neuropeptides hypothalamic arcuate nucleus neuroprogenitor cells AMPK activator |
| title | Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK |
| title_full | Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK |
| title_fullStr | Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK |
| title_full_unstemmed | Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK |
| title_short | Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK |
| title_sort | maternal high fat diet programs male mice offspring hyperphagia and obesity mechanism of increased appetite neurons via altered neurogenic factors and nutrient sensor ampk |
| topic | developmental programming neuropeptides hypothalamic arcuate nucleus neuroprogenitor cells AMPK activator |
| url | https://www.mdpi.com/2072-6643/12/11/3326 |
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