Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats #

Abstract

Chronic ethanol feeding decreases expression of adiponectin by adipocytes and circulating adiponectin. Adiponectin treatment during chronic ethanol feeding prevents liver injury in mice. Chronic ethanol feeding also increases oxidative and endoplasmic reticulum (ER) stress in adipose tissue. Here we tested the hypothesis that supplemental taurine, an amino acid that functions as a chemical chaperone/osmolyte and enhances cellular antioxidant activity, would prevent ethanol-induced decreases in adiponectin expression and attenuate liver injury. Serum adiponectin concentrations decreased as early as 4 to 7 days after feeding rats a 36% ethanol diet. This rapid decrease was associated with increased oxidative, but not ER, stress in subcutaneous adipose tissue. Taurine prevented ethanol-induced oxidative stress and increased inflammatory cytokine expression in adipose tissue. Ethanol feeding also rapidly decreased expression of transcription factors regulating adiponectin expression (CCAAT/enhancer binding protein ␣; peroxisome proliferator-activated receptor ␣/␥) in subcutaneous adipose tissue. Taurine prevented the ethanol-induced decrease in CCAAT/enhancer binding protein ␣ and peroxisome proliferator-activated receptor ␣, normalizing adiponectin messenger (m)RNA and serum adiponectin concentrations. In the liver, taurine prevented ethanol-induced oxidative stress and attenuated tumor necrosis factor ␣ expression and steatosis, at least in part, by increasing expression of genes involved in fatty acid oxidation. Conclusion: In subcutaneous adipose tissue, taurine decreased ethanol-induced oxidative stress and cytokine expression, as well as normalized expression of adiponectin mRNA. Taurine prevented ethanol-induced decreases in serum adiponectin; normalized adiponectin was associated with a reduction in hepatic oxidative stress, tumor necrosis factor ␣ expression, and steatosis. Taken together, these data demonstrate that taurine has important protective effects against ethanol-induced tissue injury in both adipose and liver tissue.

Identification of a Cytochrome P4502E1/Bid/C1q-dependent Axis Mediating Inflammation in Adipose Tissue after Chronic Ethanol Feeding to Mice

“…6). Ethanol exposure is associated with the development of oxidant stress in a number of tissues (12) including adipose tissue (3,4). In the liver, ethanol-induced oxidant stress is due at least in part to ethanol metabolism via CYP2E1 (12).…”

“…Total RNA was reverse-transcribed using the RETROscript kit (Ambion). Real-time PCR amplification was performed using the SYBR Green PCR Master Mix (Applied Biosystems) in an Mx3000p PCR machine, as previously described (4). The primer sequences used were: TNF␣ forward (F) 5Ј-CCCTCACACTCAGATCATCTTCT-3Ј, reverse (R) 5Ј-GCTACGACGTGGGCTACAG-3Ј; IL-6 F 5Ј-TAGTCCTTCCTACCCCAATTTCC-3Ј, R 5Ј-TTGGTC-CTTAGCCACTCCTTC-3Ј; MCP-1 F 5Ј-AGGTCCCTGT-CATGCTTCTG-3Ј, R 5Ј-TCTGGACCCATTCCTTCTTG-3Ј; F4/80 F 5Ј-CCCCAGTGTCCTTACAGAGTG-3Ј, R 5Ј-GT-GCCCAGAGTGGATGTCT-3Ј; CD11b F 5Ј-ATGGACGCT- …”

“…After chronic ethanol feeding, indicators of oxidative stress, such as 4-hydroxynonenal, are detected in adipose tissue (3,4). Expression of inflammatory cytokines and macrophage infiltration into adipose tissue are also increased, and adipocytes exhibit insulin resistance (3).…”

“…Many of the pathophysiological effects of ethanol are dependent on ethanol metabolism, particularly via cytochrome P4502E1 (CYP2E1). CYP2E1 is induced in response to chronic exposure to high concentrations of ethanol; expression of CYP2E1 is greatest in the liver, but expression is also increased in adipose tissue of rats after ethanol feeding (4).…”

C/EBP beta and C/EBP delta expression is elevated in the early phase of ethanol-induced hepatosteatosis in mice

“…Previous studies have examined the effect of ethanol on C/EBPs in animals and in cell cultures, but the results are inconsistent [10,19,20] . In addition, little or no information is available about the effect of ethanol on C/EBP delta.…”