The US prevalence of obesity has risen from less than 20% to over 40% in last the 25 years despite all efforts to control it. Obesity represents a major health challenge because it substantially increases the risk of leading causes of death, including diabetes, heart disease, stroke, and several cancers, as well as dementia and poorer mental health, thereby contributing to a decline in both quality of life and life expectancy. Obesity is also associated with increasingly abnormal function of adipose tissue which contributes to the development of insulin resistance. Prevention and treatment through lifestyle and public health intervention have not been successful in the long term. Currently, the most effective and long-lasting treatment for severe obesity is bariatric surgery (a.k.a. weight-loss surgery). Of course, pharmacological agents have also been explored, though these have historically run into safety concerns. One target under active research is the endocannabinoid system, the antagonism of which reduces food intake resulting in weight-loss. However, this effect is driven by central mechanisms, and the role of the peripheral endocannabinoid system in metabolism is much less understood. The work reported in this dissertation led to novel findings in obesity research. The first chapter provides an overview of obesity, hunger, appetite, and the metabolic role of adipose tissue. It also introduces the endocannabinoid system as a link between food intake and metabolism, and further explores the role of cannabinoid action in adipose tissue. The second chapter describes a clinical study of the impact of vertical sleeve gastrectomy on subjective hunger and appetite. This study revealed that 12-weeks after vertical sleeve gastrectomy surgery, when subjects still have obesity, subjects’ ratings of hunger and appetite do not significantly decline over the course of the day as they did before surgery. Interestingly, this was observed in parallel with post-surgery fasting levels of leptin and ghrelin being altered in favor of increased food intake. Lastly, the third chapter pivots from the clinic to a novel investigation of cannabinoid action in primary murine white adipose tissue. Utilizing mRNA-sequencing and qRT-PCR methods, the study presents evidence that that the synthetic cannabinoid WIN 55,212-2 inhibited expression of insulin and calcium signaling pathway genes and activity in primary adipose tissue. In addition, assessments of lipid metabolism and insulin signaling linked the attenuated antilipolytic action of insulin to the suppression of insulin-dependent Akt phosphorylation by WIN 55,212-2. Taken together, the chapters of this dissertation allude to the immense complexity of obesity, explore the links between neuroendocrine signaling and food intake, and highlight the roles of adipose tissue and the endocannabinoid system as major players in the regulation of energy metabolism.