Table 1.

An overview of some of the effects of CB₁ activation in various organs and body systems that play a role in metabolism. The combined effect of peripheral CB₁ activation is to promote appetite, and energy storage and preservation.

System/Organ	Tissue/Cell	Effect of CB1 Activation
GI system	Oral cavity	CB1 receptors are expressed in type II taste cells that also express the sweet-taste receptor, and their activation increases sweet sensitivity [35]. CB1 receptors on the tongue increase gustatory nerve responses [35].
	Stomach	CB1 is expressed on acid-secreting parietal cells [36]. CB1 activation decreases gastric secretion and acetylcholine release [37]. CB1 activation delays gastric emptying [38]. CB1 is expressed in ghrelin-positive gastric mucosal cells [39]. CB1 activation enhances ghrelin release from the stomach [40].
	I cells of the small intestine	CB1 is expressed in enteroendocrine cells [41]. CB1 inhibits the secretion of the satiation hormone cholecystokinin [41].
	Intestines	CB1 activation slows GI motility, particularly stress-induced motility [42,43]. CB1 activation prevents increased intestine permeability (leaky guts) [44]. Intestinal CB1 activation important for palatability of high fat high sugar foods [45]. CB1 deletion in intestinal epithelium reduces western diet preferences [24].
	Afferent vagus nerves	CB1 receptors are expressed on vagal terminals [46,47]. Fasting increases CB1 expression on vagal afferent neurons [47]. The induction of feeding by peripherally CB1 activation is inhibited by vagal ablation [48]. CB1 activation modulates gastric vagal afferent mechanosensitivity to stretch/distension (leading to feeling of fullness) [39].
	Microbiome	CB1 receptor antagonism [49] or THC [50] increases Akkermansia muciniphila. Probiotic treatment increases CB1 and/or CB2 expression [51,52].
Fat tissue	Adipocytes	CB1 is expressed on adipocytes [53]. CB1 deletion protects adult mice from diet-induced obesity [21]. CB1 increases adipocyte differentiation and adipogenesis [54]. CB1 activation increases PPARγ expression, a major regulator of adipose function [52]. CB1 enhances fat storage and reduces lipolysis [54,55]. CB1 decreases adiponectin production [54,56]. CB1 reduces alternative macrophage activation [21].
	White adipocyte mitochondria	CB1 activation decreases mitochondrial respiration and oxygen consumption [57,58].
	Brown adipose tissue (BAT)	CB1 is upregulated during activation of BAT [59,60]. CB1 antagonism increases expression of uncoupling protein 1 (UCP-1) [61].
Liver	Hepatocytes	CB1 activation increases lipogenesis [62] CB1 activation increases fatty acid synthesis [62]. CB1 activation induces gluconeogenesis [63]. CB1 activation promotes liver regeneration by increasing mitotic progression [64]. CB1 knock-out mice are protected against diet-induced lipogenesis and steatosis [65].
Pancreas	Pancreatic β-cells	CB1 activation stimulates basal and glucose-dependent insulin secretion [66,67]. CB1 activation impedes insulin-stimulated IR autophosphorylation [68]. CB1 receptors can lead to β-cell death [69].
Muscle	Skeletal muscle cells	CB1 expression increases during skeletal muscle cell differentiation [31,33]. CB1 activation decreases insulin-mediated glucose uptake [31]. CB1 knockdown improves mitochondrial performance, increases whole-body muscle energy expenditure, and improves physical endurance [23]. CB1 receptor knockdown prevents diet-induced and age-induced insulin resistance [23].
	Myotubules	CB1 activation prevents myotubule formation [33]. CB1 activation inhibits sarcoplasmic Ca2+ release [70].
	Skeletal muscle satellite cells	CB1 activation inhibits satellite cell differentiation [34].
	Muscle Mitochondria	CB1 receptors regulates mitochondrial oxidative activity [20].