Gut-Brain Cross-Talk in Metabolic Control

Abstract

Because human energy metabolism evolved to favor adiposity over leanness, the availability of palatable, easily attainable, and calorically dense foods has led to unprecedented levels of obesity and its associated metabolic co-morbidities that appear resistant to traditional lifestyle interventions. However, recent progress identifying the molecular signaling pathways through which the brain and the gastrointestinal system communicate to govern energy homeostasis, combined with emerging insights on the molecular mechanisms underlying successful bariatric surgery, gives reason to be optimistic that novel precision medicines that mimic, enhance, and/or modulate gut-brain signaling can have unprecedented potential for stopping the obesity and type 2 diabetes pandemics.

Dynamics of Gut-Brain Communication Underlying Hunger

“…Nutrient detection in the gut triggers the release of many hormones that inhibit food intake (Clemmensen et al, 2017; Tolhurst et al, 2012). To investigate whether these satiation signals are able to regulate AgRP neuron activity, we fasted mice overnight, challenged them with IP injection of a panel of candidate hormones, and then measured the response by photometry.…”

“…This communication is mediated by a web of hormones, metabolites, and ascending neural signals that report on the nutritional state of the body (Cummings and Overduin, 2007). The targets of these signals are thought to be neurons in the hypothalamus and related structures that integrate this information in order to generate a central representation of physiologic state (Clemmensen et al, 2017). While this gut-brain communication has been studied for decades by manipulating the signals and sensors that comprise the afferent pathways (Sohn et al, 2013), we still know remarkably little about how interoception is represented in the dynamics of the target neural circuits.…”

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

“…Current‐day society is characterised by a dietary environment that, as Clemmensen and colleagues recently stated, “supersedes peripherally derived satiation and adiposity signals, exploits the limbic system, is ‘unnaturally’ energy‐dense and hyperpalatable, and comes in virtually unlimited quantities” . 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 .…”

Effects of endurance training and herb supplementation on tissue nesfatin-1/nucleobindin-2 and ghrelin mRNA expression

“…Although the action of nesfatin-1 on food intake behavior and body weight get much more attention , but on the basis of published data nesfatin-1 could act as a biomarkers and also has an anti-hyperglycemic, anti-inflammatory, neuroendocrine regulator, and lowering body fat via appetite suppression, and metabolic and cardiovascular actions [9,[19][20][21][22][23].The levels of tissue and plasma nesfatin-1 could be affected under nutritional status (fasting and fed states, restraint stress abdominal surgery, high fat diets, , , glycemic state, different nutrient manipulation [9,24,25]. In contrast to the nesfatin-1 whose recognized and discovered as an anorexigenic peptide, ghrelin is discovered in peripheral tissue (fundus part of stomach) and introduced as an orexigenic peptide, but according to the several published studies this peptide also centrally expresses [26][27][28].…”