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.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—A Condition Associated with Heightened Sympathetic Activation

“…Chronic portal oxygen depletion limits adenosine triphosphate (ATP) production and induces adenosine release that further increases the hepatic sympathetic tone, triggering the “hepato-renal reflex”. Increased sympathetic activation in the liver results in the reduction of blood flow and increase in hepatic arteriolar resistance, which causes reflex renal sympathetic activation, with consequent renal arteriolar vasoconstriction and renin-angiotensin-aldosterone system (RAAS) activation [ 55 ]. The hepato-renal reflex mediated RAAS activation further decreases the renal blood flow, glomerular filtration and increases systemic sodium retention.…”

“…The peri-venous hepatocellular lipid accumulation in MAFLD, compromises the oxygen delivery to the hepatocytes [ 55 ]. In addition, the low ATP status in MetS also contributes to metabolic inflexibility and impaired β-oxidation and further accentuates the hepatic lipid accumulation in MAFLD.…”

“…Additionally, the metabolic surgeries performed in morbid obesity either bypasses or minimize nutrient contact, lowering splanchnic oxygen demand and enhances portal oxygen availability. This resulted in increased ATP and reduced uric acid production which blunts the hepato-renal reflex and the sympathetic activation following bariatric surgery [ 55 , 60 ].…”

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications

“…In the first concept, intrahepatic oxygen zonation is intensified when increased postprandial splanchnic oxygen consumption is compounded by impaired hepatic microcirculation due to hepatocellular swelling from lipid accumulation, resulting in hypoxia, reduced ATP production, and the increased release of adenosine, which is believed to stimulate the hepatorenal reflex, leading to reduced renal blood flow [ 89 ]. This process is aggravated by the ingestion of fructose, which is metabolized by consuming ATP, resulting in the production of more adenosine [ 89 ]. Apparently, these early hemodynamic and metabolic changes may be reverted by dietary changes or bariatric surgery procedures.…”

Papel da alça ECA2/Ang 1-7/Mas na prevenção da doença hepática gordurosa não alcoólica por meio do treinamento físico aeróbio

“…(GENTILE et al, 2015;WIDER, 2016;BROUWERS et al, 2017;GEISLER et al, 2017), escolhemos o mesmo modelo para investigar o efeito do TFA sobre a estrutura e a função hepática.…”