Editorial: Insights in integrative physiology: 2021

Abstract

Editorial on the Research Topic Insights in integrative physiology: 2021 The past decade has seen significant advancements in the field of Integrative Physiology. This series, Insights in Integrative Physiology 2021, published in Frontiers in Physiology, aims to highlight these developments, providing a comprehensive overview of what has been achieved and future challenges, in order to inform, inspire and provide direction and guidance to researchers in the field. The series is unified by the exploration of interconnected metabolic, endocrine, immune, cardiovascular, respiratory, renal, and neural systems that work together to maintain homeostasis. Each paper offers a distinct perspective on this topic. And while the papers are organised thematically in this editorial, it should be apparent to readers that it is challenging to examine each system independently of the others. As a perfect start to the Research Topic, the commentary provided by Curtis provides a perspective on the importance of integrative physiology education, seen through the lens of angiotensin II research over the last 30 years. The author argues that the field of physiology has shifted towards the cellular, molecular and genetic, resulting in inadequate understanding of whole body integrative physiological function. The author contends that while students have extensive knowledge of the molecular biology of angiotensin signalling, they do not know about the outcome of that signalling, which is crucial for understanding the interrelated and complementary neural, cardiovascular, renal, and endocrine elements. The take home message is that integrative physiology should be given more attention to ensure its significance and appreciation are reinforced in both education and research. The paper by Simões-Alves et al. reviews the cardiometabolic effects resulting from postnatal hyperlipidic diets in protein-restricted subjects, and the epigenetic repercussions occasioned by a phenomenon termed nutritional transition. The authors describe a trend over the last decade whereby maternal protein undernutrition during pregnancy and lactation followed by a high-fat diet has been linked to the development of cardiometabolic diseases in the offspring. Nutritional transition is associated with growth restriction, increased blood pressure, dyslipidaemia, and insulin resistance, as well as sympathetic overactivity, hypertension, and disruptions in respiratory control. They examine the epigenetic mechanisms proposed to be involved in these cardiometabolic effects including changes in DNA methylation and increased transcription of genes involved in the regulation of blood pressure and insulin sensitivity. The paper highlights how our understanding of complex epigenetic mechanisms may help understand cardiovascular disease risk with intergenerational and transgenerational implications. Original research in this Research Topic also examines the consequences of protein restriction during sensitive windows of postnatal growth and how this can also predispose to cardiovascular disease. Oliveira Ferreira et al. demonstrate that the peri-pubertal period in male rats is a sensitive period that is vulnerable to the programming of autonomic dysfunction and cardiovascular remodelling in adulthood. Moreover, this research team revealed that a brief exposure to the low protein diet and subsequent catch-up growth evoked elevated peripheral sympathetic activity (hypertension with increased arterial pressure low frequency power spectral density) and altered redox state in both the brainstem and the heart that led to the onset of cardiac remodelling. The topic also attracted a number of in-depth reviews covering other aspects of metabolism. Shi and Qiu reviewed some of the newer reports on myocardial energy substrate metabolism, cardiac metabolic remodelling during exercise and cardiac development. Tan and Naylor reviewed how new knowledge of metabolic, protein and transcriptional pathways that occur in breast and prostate cancer can be influenced by modifiable lifestyle factors to change cancer cell physiology to reduce risk and benefit prognosis. Blood pressure regulation and sodium-water homeostasis are modulated by the mineralocorticoid receptor (MR) through endogenous aldosterone and corticosteroids. For this reason, MR antagonists have received considerable attention as valuable first line therapies for hypertension and heart failure. However, beyond the vasculature, chronic activation of MR in cardiomyocytes is shown by Bienvenu et al. to adversely alter extracellular matrix composition and myocardial inflammatory state, redox balance, intracellular ion composition and apoptosis, leading to increased vulnerability of the heart to ischaemia. This mini-review presents compelling evidence for sex-specific differences in MR signaling involving estrogen receptor interactions that need to be further explored if we are to reduce the greater heart failure burden that exists in women. Another key process that regulates sodium-water homeostasis is osmoregulation and vital to the regulation of osmolarity is the neuroendocrine supraoptic nucleus (SON) of the hypothalamus. Mecawi et al. provide an overview of the current understanding of the mechanisms that regulate plasma osmolarity within the SON, including osmosensing, transcriptomic plasticity of during long term hyperosmolality and the somatodendritic release of neuropeptides in response to osmotic challenge. Touching on several themes within the Research Topic Badoer reviews the important contributions of circulating cytokines and locally-induced inflammation in the brain and overactivation of the sympathoadrenal and central renin angiotensin (RAS) systems in the promotion and potentiation of autonomic dysfunction in heart failure. The work highlights likely reasons why anti-inflammatory therapies have often been ineffective in preventing central inflammation in heart failure and the...