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.

Keywords: Food Intake; Hepatic Portal Vein; Nutrient Sensing; Reward.

Figure 1

HPV nutrient sensing and feeding behavior. Schematic depicting putative connectivity between the HPV, sensory afferents, and key feeding centers in the brain. The portal vein begins at the confluence of the superior mesenteric and splenic veins, carrying blood from the intestines and spleen. Vagal and spinal afferents that innervate the entire hepatic portal area relay this information to brain, likely to the dorsal vagal complex (DVC). Glucose infused in the portal vein modulates activity in this brainstem region in addition to feeding centers within the hypothalamus (such as the arcuate hypothalamic nucleus [ARC] and LH) and results in increased dopamine (DA) release in the striatum, including in the nucleus accumbens (NAc). Glucose detected in the portal vein ultimately decreases feeding behavior. The HPV box depicts the anatomy of the vein, which consists of 4 layers (from outer to inner): (1) tunica adventitia, a layer of connective tissues with collagen and elastic fibrils; (2 and 3) tunica media, which comprises a longitudinal smooth muscle layer (2) and a layer of circular smooth muscle (3); and (4) tunica interna, a thin layer of endothelial cells that line the lumen of the HPV. Sensory afferents innervate the outer 3 layers (1–3), and it remains unclear how far they project toward the lumen, and where glucose sensors (SGLT3 and GLUT2) are expressed. Hormonal and metabolic pathways (not depicted here) also contribute to energy balance control and likely interact with portal glucose sensing to influence feeding behavior.