Glucose Sensing in the Hepatic Portal Vein and Its Role in Food Intake and Reward

Abstract

The detection of nutrients in the gut influences ongoing and future feeding behavior as well as the development of food preferences. In addition to nutrient sensing in the intestine, the hepatic portal vein plays a considerable role in detecting ingested nutrients and conveying this information to brain nuclei involved in metabolism, learning, and reward. Here, we review mechanisms underlying hepatic portal vein sensing of nutrients, particularly glucose, and how this is relayed to the brain to influence feeding behavior and reward. We additionally highlight several gaps where future research can provide new insights into the effects of portal nutrients on neural activity in the brain and feeding behavior. The detection of nutrients in the gut influences ongoing and future feeding behavior as well as the development of food preferences. In addition to nutrient sensing in the intestine, the hepatic portal vein plays a considerable role in detecting ingested nutrients and conveying this information to brain nuclei involved in metabolism, learning, and reward. Here, we review mechanisms underlying hepatic portal vein sensing of nutrients, particularly glucose, and how this is relayed to the brain to influence feeding behavior and reward. We additionally highlight several gaps where future research can provide new insights into the effects of portal nutrients on neural activity in the brain and feeding behavior. SummaryWe review mechanisms underlying hepatic portal vein sensing of nutrients, particularly glucose, and its influence on feeding behavior. We additionally highlight gaps where future research can refine our knowledge of how portal nutrients modulate brain activity and food intake. We review mechanisms underlying hepatic portal vein sensing of nutrients, particularly glucose, and its influence on feeding behavior. We additionally highlight gaps where future research can refine our knowledge of how portal nutrients modulate brain activity and food intake. Food intake is governed by a complex set of biological mechanisms involving the body and brain.1Andermann M.L. Lowell B.B. Toward a wiring diagram understanding of appetite control.Neuron. 2017; 95: 757-778Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar, 2Clemmensen C. Müller T.D. Woods S.C. et al.Gut-brain cross-talk in metabolic control.Cell. 2017; 168: 758-774Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar, 3Shechter A. Schwartz G.J. Gut-brain nutrient sensing in food reward.Appetite. 2018; 122: 32-35Crossref PubMed Scopus (21) Google Scholar In particular, nutrient sensing in the gastrointestinal tract is fundamental to regulating energy homeostasis and feeding behavior.2Clemmensen C. Müller T.D. Woods S.C. et al.Gut-brain cross-talk in metabolic control.Cell. 2017; 168: 758-774Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar The body contains multiple organs with a wide variety of transporters and sensors that detect several nutrients, including but not limited to carbohydrates, proteins, and fats. The detection of glucose, the main source of energy for all cells in the body, is of particular metabolic importance. Circulating blood glucose concentrations are maintained within a tight range, and major fluctuations can cause serious disturbances such as blurred vision, fatigue, and in extreme cases, loss of consciousness or death.4Wasserman D.H. Four grams of glucose.Am J Physiol Endocrinol Metab. 2009; 296: E11-E21Crossref PubMed Scopus (257) Google Scholar To maintain glucose homeostasis, the body has specialized systems for glucose sensing.5Stanley S. Moheet A. Seaquist E.R. Central mechanisms of glucose sensing and counterregulation in defense of hypoglycemia.Endocr Rev. 2019; 40: 768-788Crossref PubMed Scopus (44) Google Scholar, 6Verberne A.J.M. Sabetghadam A. Korim W.S. Neural pathways that control the glucose counterregulatory response.Front Neurosci. 2014; 8: 38Crossref PubMed Scopus (99) Google Scholar, 7Wachsmuth H.R. Weninger S.N. Duca F.A. Role of the gut-brain axis in energy and glucose metabolism.Exp Mol Med. 2022; 54: 377-392Crossref PubMed Scopus (15) Google Scholar To deal with excess glucose, the body prepares for incoming nutrients with metabolic responses and mechanisms to curb additional food intake. Conversely, when energy is low, the body initiates counterregulatory processes to conserve and produce glucose. To this end, levels of glucose (and other nutrients) are sensed in the gastrointestinal tract and hepatic portal area and trigger the initiation of appropriate metabolic, digestive, or counterregulatory processes. In turn, the signals generated by peripheral nutrient detection are communicated to the brain to modulate current and future food intake. After absorption from the gastrointestinal tract, nutrients enter the circulatory system through mesenteric capillary beds that flow into the hepatic portal vein (HPV). The HPV is exposed to the largest range of concentrations of glucose in the body.8Croset M. et al.Rat small intestine is an insulin-sensitive gluconeogenic organ.Diabetes. 2001; 50: 740-746Crossref PubMed Google Scholar, 9Soty M. Gautier-Stein A. Rajas F. et al.Gut-brain glucose signaling in energy homeostasis.Cell Metab. 2017; 25: 1231-1242Abstract Full Text Full Text PDF PubMed Google Scholar, 10Strubbe J.H. Bruggink J.E. Steffens A.B. Hepatic portal vein cannulation for infusion and blood sampling in freely moving rats.Physiol Behav. 1988; 65: 885-887Crossref Scopus (14) Google Scholar Therefore, the HPV may be the most important area in the body to sense glucose levels and trigger appropriate behavioral and physiological changes. Here, we focus on glucose sensing within the HPV and how it influences food intake. After briefly summarizing the anatomy of the HPV, we review literature on the effects of HPV glucose sensing on food intake. We additionally discuss putative gut-brain mechanisms that relay glucose-related information to the brain to influence feeding behavior and reward processing. Last, we discuss current gaps in knowledge and future research directions that will lead to a better understanding of portal glucose sensing and the portal control of feeding behavior. 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Bruggink J.E. Steffens A.B. Hepatic portal vein cannulation for infusion and blood sampling in freely moving rats.Physiol Behav. 1988; 65: 885-887Crossref Scopus (14) Google Scholar feeding effects with HPV can be to nutrient sensing that within or of this of the HPV, it not the that nutrient sensing within as M. of the influence of an hepatic on Behav. PubMed Scopus Google Scholar the to that of glucose into the HPV in the cause of an ongoing this that portal glucose food intake including and M. of the influence of an hepatic on Behav. PubMed Scopus Google Scholar, of is by and glucose Behav. PubMed Scopus Google Scholar, The of glucose on as a of feeding and infusion Behav. PubMed Scopus Google Scholar, of food intake in the absorption of glucose into the intestine or PubMed Scopus Google Scholar, levels and peripheral mechanisms of of J PubMed Scopus Google Scholar, et of infusion of glucose and on food intake in rats.Physiol Behav. PubMed Scopus Google Scholar, M. M. 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