Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats
Intrauterine growth retardation (IUGR) poses a high risk for developing late-onset, non-obese type 2 diabetes (T2DM). The exact mechanism underlying this phenomenon is unknown, although the contribution of the central nervous system is recognized. The main hypothalamic nuclei involved in the homeost...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.828571/full |
| _version_ | 1818317899966709760 |
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| author | Máté Durst Katalin Könczöl Klementina Ocskay Klaudia Sípos Péter Várnai Anett Szilvásy-Szabó Csaba Fekete Zsuzsanna E. Tóth |
| author_facet | Máté Durst Katalin Könczöl Klementina Ocskay Klaudia Sípos Péter Várnai Anett Szilvásy-Szabó Csaba Fekete Zsuzsanna E. Tóth |
| author_sort | Máté Durst |
| collection | DOAJ |
| description | Intrauterine growth retardation (IUGR) poses a high risk for developing late-onset, non-obese type 2 diabetes (T2DM). The exact mechanism underlying this phenomenon is unknown, although the contribution of the central nervous system is recognized. The main hypothalamic nuclei involved in the homeostatic regulation express nesfatin-1, an anorexigenic neuropeptide and identified regulator of blood glucose level. Using intrauterine protein restricted rat model (PR) of IUGR, we investigated, whether IUGR alters the function of nesfatin-1. We show that PR rats develop fat preference and impaired glucose homeostasis by adulthood, while the body composition and caloric intake of normal nourished (NN) and PR rats are similar. Plasma nesfatin-1 levels are unaffected by IUGR in both neonates and adults, but pro-nesfatin-1 mRNA expression is upregulated in the hypothalamus of adult PR animals. We find that centrally injected nesfatin-1 inhibits the fasting induced neuronal activation in the hypothalamic arcuate nucleus in adult NN rats. This effect of nesfatin-1 is not seen in PR rats. The anorexigenic effect of centrally injected nesfatin-1 is also reduced in adult PR rats. Moreover, chronic central nesfatin-1 administration improves the glucose tolerance and insulin sensitivity in NN rats but not in PR animals. Birth dating of nesfatin-1 cells by bromodeoxyuridine (BrDU) reveals that formation of nesfatin-1 cells in the hypothalamus of PR rats is disturbed. Our results suggest that adult PR rats acquire hypothalamic nesfatin-1-resistance, probably due to the altered development of the hypothalamic nesfatin-1 cells. Hypothalamic nesfatin-1-resistance, in turn, may contribute to the development of non-obese type T2DM. |
| first_indexed | 2024-12-13T09:44:40Z |
| format | Article |
| id | doaj.art-fac0f0f12a734837a72a38d29440d4c3 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T09:44:40Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-fac0f0f12a734837a72a38d29440d4c32022-12-21T23:52:06ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-03-011610.3389/fnins.2022.828571828571Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese RatsMáté Durst0Katalin Könczöl1Klementina Ocskay2Klaudia Sípos3Péter Várnai4Anett Szilvásy-Szabó5Csaba Fekete6Zsuzsanna E. Tóth7Laboratory of Neuroendocrinology and in situ Hybridization, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, HungaryLaboratory of Neuroendocrinology and in situ Hybridization, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, HungaryLaboratory of Neuroendocrinology and in situ Hybridization, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, HungaryLaboratory of Neuroendocrinology and in situ Hybridization, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University, Budapest, HungaryLaboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Neuroendocrinology and in situ Hybridization, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, HungaryIntrauterine growth retardation (IUGR) poses a high risk for developing late-onset, non-obese type 2 diabetes (T2DM). The exact mechanism underlying this phenomenon is unknown, although the contribution of the central nervous system is recognized. The main hypothalamic nuclei involved in the homeostatic regulation express nesfatin-1, an anorexigenic neuropeptide and identified regulator of blood glucose level. Using intrauterine protein restricted rat model (PR) of IUGR, we investigated, whether IUGR alters the function of nesfatin-1. We show that PR rats develop fat preference and impaired glucose homeostasis by adulthood, while the body composition and caloric intake of normal nourished (NN) and PR rats are similar. Plasma nesfatin-1 levels are unaffected by IUGR in both neonates and adults, but pro-nesfatin-1 mRNA expression is upregulated in the hypothalamus of adult PR animals. We find that centrally injected nesfatin-1 inhibits the fasting induced neuronal activation in the hypothalamic arcuate nucleus in adult NN rats. This effect of nesfatin-1 is not seen in PR rats. The anorexigenic effect of centrally injected nesfatin-1 is also reduced in adult PR rats. Moreover, chronic central nesfatin-1 administration improves the glucose tolerance and insulin sensitivity in NN rats but not in PR animals. Birth dating of nesfatin-1 cells by bromodeoxyuridine (BrDU) reveals that formation of nesfatin-1 cells in the hypothalamus of PR rats is disturbed. Our results suggest that adult PR rats acquire hypothalamic nesfatin-1-resistance, probably due to the altered development of the hypothalamic nesfatin-1 cells. Hypothalamic nesfatin-1-resistance, in turn, may contribute to the development of non-obese type T2DM.https://www.frontiersin.org/articles/10.3389/fnins.2022.828571/fullIP-ITTIP-GTTneuronal birth datingcFosarcuate nucleusnesfatin-1 |
| spellingShingle | Máté Durst Katalin Könczöl Klementina Ocskay Klaudia Sípos Péter Várnai Anett Szilvásy-Szabó Csaba Fekete Zsuzsanna E. Tóth Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats Frontiers in Neuroscience IP-ITT IP-GTT neuronal birth dating cFos arcuate nucleus nesfatin-1 |
| title | Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats |
| title_full | Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats |
| title_fullStr | Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats |
| title_full_unstemmed | Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats |
| title_short | Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats |
| title_sort | hypothalamic nesfatin 1 resistance may underlie the development of type 2 diabetes mellitus in maternally undernourished non obese rats |
| topic | IP-ITT IP-GTT neuronal birth dating cFos arcuate nucleus nesfatin-1 |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.828571/full |
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