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 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 the loss of appetite or dietary restriction.

Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches

“…The hepatic origin of this reflex was confirmed by transection of the hepatic vagal nerves or spinal cord that prevented the effect on the renal sympathetic nerves whereas unilateral renal denervation (RDN) prevented the effect only in the denervated kidney [63]. The hepato-renal reflex mechanism in response to decreased hepatic blood flow is further supported by denervation experiments of the liver and/or the kidneys [62–64]. Another factor that induces this mechanism is adenosine.…”

“…Increased hepatic sympathetic tone results in decreased hepatic blood flow and increased hepatic resistance, which in turn cause reflex activation of renal sympathetic nerves with the consequence of renal vasoconstriction and stimulation of the RAS [62]. Activation of the hepatorenal sympathetic reflex causes an immediate decrease in renal blood flow, glomerular filtration rate and urine flow and enhanced sodium retention.…”

“…In addition to other mechanisms described above, various types of metabolic surgery that bypasses/minimizes the nutrient contact significantly, lowers splanchnic O 2 demands and enhance portal O 2 availability. This results in increased ATP and reduced uric acid production and blunts the hepato-renal reflex, thereby reducing sympathetic overdrive following bariatric surgery [62,69]. The postulated mechanism of hepatic regulation of BP is depicted in Fig.…”

Maternal Venous Hemodynamic Dysfunction in Proteinuric Gestational Hypertension: Evidence and Implications

“…From this perspective, it is hypothesized that venous congestion in preeclampsia can occur via 3 different pathways, alone or in combination: (a) venous hypertension, associated with increased venous vascular tone, (b) venous overfill in a system functioning at maximum capacitance, and (c) increased external venous pressure as in intra-abdominal hypertension syndrome. Each of these mechanisms can trigger a cascade of cardiovascular humoral, paracrine of neural reflex responses with subsequent hypertension and reduced organ perfusion [170,171]. Interestingly, from the clinical point of view, these three mechanisms go very well with the reported subtypes of preeclampsia and their intrinsic longitudinal hemodynamic changes: (a) EPE with a sudden onset and fulminant course, often ending in a premature birth of an neonate small for gestational age [172,173], (b) one of two variants of LPE [174], in which a cross over occurs from an early gestational high volume/low resistance to a late gestational low volume/high resistance circulation [175], and (c) the second variant of LPE, where a high volume/low resistance circulation persists throughout the course of pregnancy in a population of mainly obese women [176].…”

Erratum: Metabolic syndrome and the hepatorenal reflex

“…In the article titled, “Metabolic syndrome and the hepatorenal reflex” published as elocation ID 83, in vol. 7 of Surgical Neurology International,[ 1 ] all the reference numbers cited in the text of the article are incorrect. The article was republished for correcting the reference numbers cited in the article.…”