Leptin and Melanocortin Signaling Mediates Hypertension in Offspring From Female Rabbits Fed a High-Fat Diet During Gestation and Lactation

Frontiers in Physiology

Yusuke Sata¹  Geoffrey A. Head²  Kyungjoon Lim³  Francine Z. Marques⁷  Cindy Gueguen⁸  Kristy L. Jackson⁸  Sandra L. Burke⁸  James A. Armitage⁹ 

[1] Department of Cardiology, Alfred Hospital, Melbourne, VIC, Australia;Department of Pharmacology, Monash University, Clayton, VIC, Australia;Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia;Faculty of Medicine, Nursing and Health Sciences, Central Clinical School, Monash University, Melbourne, VIC, Australia;Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia;Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;School of Medicine (Optometry), and IMPACT Institute for Innovation in Physical and Mental Health and Clinical Translation, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia;

关键词: programming;    neuronal plasticity;    hypertension;    maternal high-fat diet;    sympathetic nerve activity;   

DOI  :  10.3389/fphys.2021.693157

来源: DOAJ

【 摘 要 】

Maternal high-fat diet in rabbits leads to hypertension and elevated renal sympathetic nerve activity (RSNA) in adult offspring but whether this is due to adiposity or maternal programming is unclear. We gave intracerebroventricular (ICV) and ventromedial hypothalamus (VMH) administration of leptin-receptor antagonist, α-melanocyte-stimulating hormone (αMSH), melanocortin-receptor antagonist (SHU9119), or insulin-receptor (InsR) antagonist to conscious adult offspring from mothers fed a high-fat diet (mHFD), control diet (mCD), or mCD offspring fed HFD for 10d (mCD10d, to deposit equivalent fat but not during development). mHFD and mCD10d rabbits had higher mean arterial pressure (MAP, +6.4 mmHg, +12.1 mmHg, p < 0.001) and RSNA (+2.3 nu, +3.2 nu, p < 0.01) than mCD, but all had similar plasma leptin. VMH leptin-receptor antagonist reduced MAP (−8.0 ± 3.0 mmHg, p < 0.001) in mCD10d but not in mHFD or mCD group. Intracerebroventricular leptin-receptor antagonist reduced MAP only in mHFD rabbits (p < 0.05). Intracerebroventricular SHU9119 reduced MAP and RSNA in mHFD but only reduced MAP in the mCD10d group. VMH αMSH increased RSNA (+85%, p < 0.001) in mHFD rabbits but ICV αMSH increased RSNA in both mHFD and mCD10d rabbits (+45%, +51%, respectively, p < 0.001). The InsR antagonist had no effect by either route on MAP or RSNA. Hypothalamic leptin receptor and brain-derived neurotrophic factor (BDNF) mRNA were greater in mHFD compared with mCD rabbits and mCD10d rabbits. In conclusion, the higher MAP in mHFD and mCD10d offspring was likely due to greater central leptin signaling at distinct sites within the hypothalamus while enhanced melanocortin contribution was common to both groups suggesting that residual body fat was mainly responsible. However, the effects of SHU9119 and αMSH on RSNA pathways only in mHFD suggest a maternal HFD may program sympatho-excitatory capacity in these offspring and that this may involve increased leptin receptor and BDNF expression.

【 授权许可】

Unknown