Analysis of Western diet, palmitate and BMAL1 regulation of neuropeptide Y expression in the murine hypothalamus and BMAL1 knockout cell models
| Autor: | Erika K. Tse, Alexandre Martchenko, Denise D. Belsham, Neruja Loganathan, Matthew N. Clemenzi, Patricia L. Brubaker |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male endocrine system medicine.medical_specialty Saturated fat Hypothalamus Palmitates Neuropeptide 030209 endocrinology & metabolism Biology Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Internal medicine Zeitgeber medicine Animals Homeostasis Neuropeptide Y Molecular Biology Cells Cultured 2. Zero hunger Mice Knockout ARNTL Transcription Factors Feeding Behavior Neuropeptide Y receptor Circadian Rhythm PER2 CLOCK Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Diet Western Saturated fatty acid Female Agouti-related peptide |
| Zdroj: | Molecular and cellular endocrinology. 507 |
| ISSN: | 1872-8057 |
| Popis: | Western diets that are high in saturated fat and sugar disrupt circadian rhythms, induce weight gain, and lead to metabolic diseases including obesity. However, the mechanistic link between altered circadian rhythms and energy homeostasis remains poorly understood. In C57BL/6J mice, consuming a Western diet for 16 weeks significantly reduced food intake (at zeitgeber 12–16), in association with decreases in hypothalamic expression of the orexigenic neuropeptides, neuropeptide Y (Npy) and agouti-related peptide (AgRP). To examine the acute effects of the most prevalent saturated fatty acid in a Western diet, palmitate, and the role of the core clock gene, Bmal1, in the regulation of hypothalamic feeding neuropeptides, we used heterogeneous and clonal BMAL1 knockout (KO) immortalized hypothalamic cell lines, expressing specific neuropeptides, derived from male (M) and female (F) mice. Both mHypoA-BMAL1-KO/F and mHypoA-BMAL1-KO/M cells demonstrated a loss of circadian rhythmicity in expression of the clock gene, Per2, as compared to wild-type (control) cultures. Loss of BMAL1 also altered the time-dependent expression of Npy and proopiomelanocortin, and disrupted AgRP rhythmicity. Furthermore, palmitate increased BMAL1 binding to the Npy promotor region, and palmitate treatment (50 μM for 24 h) stimulated Npy expression in a BMAL1-dependent manner in both heterogeneous and clonal NPY-expressing female-derived cell models. The results of this study demonstrate that circadian expression of Bmal1 serves as a mechanistic link between Western diet- and palmitate-induced disruptions of the normal rhythmic patterns in hypothalamic feeding-related neuropeptides. |
| Databáze: | OpenAIRE |
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