Signalling from the periphery to the brain that regulates energy homeostasis

Abstract

The CNS regulates body weight; however, we still lack a clear understanding of what drives decisions about when, how much and what to eat. A vast array of peripheral signals provides information to the CNS regarding fluctuations in energy status. The CNS then integrates this information to influence acute feeding behaviour and long-term energy homeostasis. Previous paradigms have delegated the control of long-term energy homeostasis to the hypothalamus and short-term changes in feeding behaviour to the hindbrain. However, recent studies have identified target hindbrain neurocircuitry that integrates the orchestration of individual bouts of ingestion with the long-term regulation of energy balance.

Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction

“…[2][3][4][5][6] Coinciding with the rise in the prevalence of obesity, substantial progress has been made in our understanding how the central nervous system receives and integrates information from a multitude of external and internal metabolic cues to generate appropriate behavioural, autonomic and endocrine output to maintain energy homeostasis. 1,7,8 As expected, obesity is hallmarked by a profound imbalance in this process.…”

“…This engineered dietary environment is a major driver of the current global obesity epidemic, which, together with the comorbidities of obesity, now poses a major societal health problem with an immense social and financial burden . Coinciding with the rise in the prevalence of obesity, substantial progress has been made in our understanding how the central nervous system receives and integrates information from a multitude of external and internal metabolic cues to generate appropriate behavioural, autonomic and endocrine output to maintain energy homeostasis . As expected, obesity is hallmarked by a profound imbalance in this process.…”

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

“…However, despite emerging reports of the post-mortem detection of the virus in the cerebrospinal fluid (CSF) (see for example (4)) or brain parenchyma of patients (5), little is known about how and under what circumstances SARS-CoV-2 infects the brain.While the possibility of CNS infection has been largely underestimated due to the common view that angiotensin converting enzyme 2 (ACE2), the only confirmed cellular receptor for SARS-CoV-2 so far (6), is absent or expressed only at very low levels in the brain (7,8), and that too exclusively in vascular cells (He et al, bioRxiv 2020; doi: https://doi.org/10.1101.088500) the majority of these studies have focused on the cerebral cortex, ignoring the fact that other regions such as the hypothalamus, are rich in ACE2 (9). Intriguingly, most major risk factors for severe COVID-19 (male sex, age, obesity, hypertension, diabetes); reviewed by (10,11); could be mediated by normal or dysfunctional hypothalamic neural networks that regulate a variety of physiological processes: sexual differentiation and gonadal hormone production, energy homeostasis, fluid homeostasis/osmoregulation and even ageing (12)(13)(14). The hypothalamus is also directly linked to other parts of the CNS involved in functions affected in COVID-19 patients, including brainstem nuclei that control fluid homeostasis, cardiac function and respiration, as well as regions implicated in the perception or integration of odor and taste (12,(14)(15)(16)(17)(18).Here, we investigated the susceptibility of the hypothalamus and related brain regions to SARS-CoV-2 infection by analyzing the expression of ACE2 and the transmembrane proteinase, serine 2 (TMPRSS2), which cleaves the SARS-CoV-2 spike (S) protein, enabling it to be internalized, from existing data from the Allen Human Brain Atlas (AHBA) (19).…”

The metabolic mind: A role for leptin and ghrelin in affect and social cognition

“…Across animals, the brain anticipates energy demands (Kim, Seeley, & Sandoval, ; Seeley & York, ), in turn orchestrating physiological and motivational changes to meet those demands, including with the help of metabolic hormones leptin and ghrelin. For example, during important life events that require intense energy use like migration, hibernation, puberty, and pregnancy, both human and animal feeding behaviors increase to intake energy, while weight status, via adipose tissue, signals how much energy is set aside for anticipated demands, e.g., a winter famine (reviews in Kaplan & Gangestad, ; McEwen & Wingfield, ).…”