Insufficient hepatic O2 in animal and human studies has been shown to elicit a hepatorenal reflex in response to increased hepatic adenosine, resulting in the stimulation of renal as well as muscle sympathetic nerve activity and activating the renin angiotensin system. Low hepatic ATP, hyperuricemia, and hepatic lipid accumulation reported in metabolic syndrome (MetS) patients may reflect insufficient hepatic O2 delivery, potentially accounting for the sympathetic overdrive associated with MetS. This theoretical concept is supported by experimental results in animals fed a high fructose diet to induce MetS. Hepatic fructose metabolism rapidly consumes ATP resulting in increased adenosine production and hyperuricemia as well as elevated renin release and sympathetic activity. This review makes the case for the hepatorenal reflex causing sympathetic overdrive and metabolic syndrome in response to exaggerated splanchnic oxygen consumption from excessive eating. This is strongly reinforced by the fact that MetS is cured in a matter of days in a significant percentage of patients by diet, bariatric surgery, or endoluminal sleeve, all of which would decrease splanchnic oxygen demand by limiting nutrient contact with the mucosa and reducing the nutrient load due to loss of appetite or dietary restriction.