Betaine supplementation protects against high-fructose-induced renal injury in rats.
High fructose intake causes metabolic syndrome, being an increased risk of chronic kidney disease development in humans and animals. In this study, we examined the influence of betaine on high-fructose-induced renal damage involving renal inflammation, insulin resistance and lipid accumulation in rats and explored its possible mechanisms. Betaine was found to improve high-fructose-induced metabolic syndrome including hyperuricemia, dyslipidemia and insulin resistance in rats with systemic inflammation. Betaine also showed a protection against renal dysfunction and tubular injury with its restoration of the increased glucose transporter 9 and renal-specific transporter in renal brush bolder membrane and the decreased organic anion transporter 1 and adenosine-triphosphate-binding cassette transporter 2 in the renal cortex in this model. These protective effects were relevant to the anti-inflammatory action by inhibiting the production of inflammatory cytokines including interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α in renal tissue of high-fructose-fed rat, being more likely to suppress renal NOD-like receptor superfamily, pyrin domain containing 3 inflammasome activation than nuclear factor κB activation. Subsequently, betaine with anti-inflammation ameliorated insulin signaling impairment by reducing the up-regulation of suppressor of cytokine signaling 3 and lipid accumulation partly by regulating peroxisome proliferator-activated receptor α/palmityltransferase 1/carnitine/organic cation transporter 2 pathway in kidney of high-fructose-fed rats. These results indicate that the inflammatory inhibition plays a pivotal role in betaine's improvement of high-fructose-induced renal injury with insulin resistance and lipid accumulation in rats.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
Chen-Yu
CY
Fan
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
Ming-Xing
MX
Wang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
Chen-Xu
CX
Ge
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
Xing
X
Wang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China. Electronic address: lijm@nju.edu.cn.
Jian-Mei
JM
Li
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China. Electronic address: kongld@nju.edu.cn.
Ling-Dong
LD
Kong
D000818:Animals; D001622:Betaine / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D050171:Dyslipidemias / Q000139:chemically induced; D005632:Fructose / Q000633:toxicity*; D033461:Hyperuricemia / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D005632:Fructose; D001622:Betaine
Betaine; Fructose; Insulin resistance; Renal inflammation; Renal injury