The accumulation of adipose tissue represents one of the characteristics of obesity, increasing the risk of developing correlated obesity diseases such as cardiovascular disease, type 2 diabetes, cancer, and immune diseases. Visceral adipose tissue accumulation leads to chronic low inflammation inducing an imbalanced adipokine secretion. Among these adipokines, Adiponectin is an important metabolic and inflammatory mediator. It is also known that adipose tissue is influenced by Orexin-A levels, a neuropeptide produced in the lateral hypothalamus. Adiponectin and Orexin-A are strongly decreased in obesity and are associated with metabolic and inflammatory pathways. The aim of this review was to investigate the involvement of the autonomic nervous system focusing on Adiponectin and Orexin-A after bariatric surgery. After bariatric surgery, Adiponectin and Orexin-A levels are strongly increased independently of weight loss showing that hormone increases are also attributable to a rearrangement of metabolic and inflammatory mediators. The restriction of food intake and malabsorption are not sufficient to clarify the clinical effects of bariatric surgery suggesting the involvement of neuro-hormonal feedback loops and also of mediators such as Adiponectin and Orexin-A.