Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5

Abstract

Increased dietary fructose in rodents recapitulates many aspects of the Metabolic Syndrome with hypertension, insulin resistance and dyslipidemia. Here we show that fructose increased jejunal NaCl and water absorption which was significantly decreased in mice whose apical chloride/base exchanger Slc26a6 (PAT1, CFEX) was knocked out. Increased dietary fructose intake enhanced expression of this transporter as well as the fructose-absorbing transporter Slc2a5 (Glut5) in the small intestine of wild type mice. Fructose feeding decreased salt excretion by the kidney and resulted in hypertension, a response almost abolished in the knockout mice. In parallel studies, a chloride-free diet blocked fructose-induced hypertension in Sprague Dawley rats. Serum uric acid remained unchanged in animals on increased fructose intake with hypertension. We suggest that fructose-induced hypertension is likely caused by increased salt absorption by the intestine and kidney and the transporters Slc26a6 and Slc2a5 are essential in this process.

Modulation of serum uric acid levels by inosine in patients with multiple sclerosis does not affect blood pressure

“…16 In addition, rats on a high fructose diet developed hypertension without an increase in the serum UA levels. 17 There is one obvious difference between our study and others. Most studies have been performed in populations with underlying vascular problems including people with metabolic syndrome, who in addition to hypertension, also have obesity, dyslipidaemia and insulin resistance.…”

Increased Fructose Associates with Elevated Blood Pressure

“…Studies in animals suggested that fructose may raise BP via several mechanisms, including stimulation of uric acid, [17][18][19] inhibition of endothelial nitric oxide synthase system, 20,21 and stimulation of the sympathetic nervous system, 22 or by directly increasing sodium absorption in the gut. 23 Although uric acid has been shown to mediate fructose-induced hypertension in rats, we could not demonstrate a relationship between high fructose intake and serum uric acid levels in this study. In our study, serum uric acid levels were not associated with increased fructose intake; neither were triglycerides, BMI, waste circumference, or diabetes.…”

“…16 Forman et al 12 studied the association between fructose and hypertension prospectively in three large cohort studies: The Nurses Health Study I (NHSI), The Nurses Health Study II (NHSII), and the Health Professionals Follow up Study (HPFS). The investigators found no association between fructose intake and hypertension; however, all of the participants in those cohorts were health care professionals and had a high intake of fruits that were included in the fructose intake scale (e.g., 23.6% of total fructose intake in NHSI was from fruits). This pattern of dietary intake does not mirror that of the general US population, in which the majority of the fructose ingested comes from added sugars rather than from fruits.…”

Association of Sweetened Beverage Intake with Incident Hypertension

“…Previous cross-sectional studies have reported an association between SSB consumption and incident hypertension: Nguyen et al found a relation between intake of sodas sweetened with HFCS and hypertension in a population of adolescents, 5 and an analysis of NHANES data found an increased prevalence of hypertension among individuals consuming higher than average amounts of fructose (≥ 74 g/d) derived mostly from SSBs. 6 Because SSBs contain fructose, which in animal studies has been shown to cause renal damage, increased gastrointestinal sodium uptake, and endothelial dysfunction, [17][18][19] it was hypothesized that the HFCS in sugary beverages was responsible for the increased risk of incident hypertension. In a prospective study, however, Forman et al found no association between total fructose intake (regardless of source) and hypertension risk.…”