Metabolic syndrome and the hepatorenal reflex

Abstract

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.

Keywords: Bariatric; cholesterol; diabetes; hepatorenal; metabolic syndrome; obesity; sympathetic.

Figure 1

The postulated etiologic mechanisms is supported by the fact that excessive eating and fructose ingestion, both of which can result in MetS, have the potential to reduce hepatic ATP production, increasing levels of adenine nucleotides that are known to stimulate the hepatorenal reflex and theoretically lead to MetS

Figure 2

Decreasing the contact of nutrient with the proximal gut by diet or bariatric surgery (including endoluminal sleeve placement) would be expected to reduce enteric oxygen consumption and improve O₂ delivery to the liver, potentially enhancing hepatic ATP production and reducing adenine nucleotide accumulation and the hepatorenal reflex

Figure 3

Reduced blood flow in the gastric artery and gastric vein following gastrectomy has the potential to improve O₂ delivery to the liver by decreasing low O₂ gastric vein contribution and increasing hepatic artery flow by limiting gastric arterial steal from the celiac artery, theoretically allowing increased hepatic ATP production and reducing adenine nucleotide accumulation and the hepatorenal reflex