Acylated ghrelin limits fat accumulation and improves redox state and inflammation markers in the liver of high‐fat‐fed rats

Abstract

Objective: Obesity commonly causes hepatic lipid accumulation that may favor oxidative stress and inflammation with negative clinical impact. Acylated ghrelin (A-Ghr) modulates body lipid distribution and metabolism, and it may exert antioxidant effects in vitro as well as systemic anti-inflammatory effects in vivo. The impact of A-Ghr on liver triglyceride content, redox state and inflammation markers in dietinduced obesity was investigated. Design and Methods: A-Ghr (200-lg=injection: HFG) or saline (HF) were administered subcutaneously twice-daily for 4 days to 12-week-old male rats fed a high-fat diet for 1 month (n 5 8-10=group).Results: Compared to lean animals, liver triglyceride accumulation occurred in HF despite enhanced phosphorylation of the lipid oxidation regulator AMPK and preserved mitochondrial enzyme activities. High triglycerides were accompanied by pro-oxidant changes in redox state and proinflammatory changes in NF-kB and TNF-alpha. A-Ghr limited liver triglyceride excess (P < 0.05 HF > HFG > Control) with concomitant activation of glutathione peroxidase and normalized redox state and cytokines. A-Ghrinduced liver changes were associated with higher plasma adiponectin and lower circulating fatty acids (P < 0.05 HFG vs. HF). Conclusions: A-Ghr limits liver triglyceride accumulation and normalizes tissue redox state and inflammation markers in diet-induced obese rats. These results suggest a favorable impact of A-Ghr on hepatic complications of diet-induced obesity.

Ghrelin Attenuated Lipotoxicity via Autophagy Induction and Nuclear Factor-κB Inhibition

“…Furthermore, the effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis [30], exerting an therapeutic effect on NAFLD. Ghrelin increases food intake and activates the AMPK signaling pathway [14,20,31]. Consistently, our study found that phosphorylation level of AMPK was reduced in the NAFLD group but restored by ghrelin without disturbing total AMPK.…”

“…Likewise, another study has reported that high levels of ghrelin are associated with low risk of developing fatty liver [23]. The most recent study has confirmed our belief that ghrelin could have a therapeutic effect in NAFLD [20]. However, the therapeutic mechanism of ghrelin in NAFLD remains largely unknown, especially the way to reduce lipid accumulation.…”

“…Ghrelin is a newly discovered peptide with various functions, including regulating energy metabolism, promoting cell proliferation [19]. Recent studies have demonstrated that ghrelin attenuates inflammatory injury [13,15,16,20,21]. Okamatsu et al have shown that serum ghrelin level is significantly elevated with liver function index in overweight children [22].…”

Hypothalamic inflammation and food intake regulation during chronic illness

“…Furthermore it is likely that this elevation of ghrelin is an attempt to suppress inflammation, as ghrelin has strong anti-inflammatory actions by inhibiting proinflammatory cytokines, augmenting anti-inflammatory cytokines [65,66] and reducing hypothalamic glial activation [67]. Furthermore, administration of ghrelin showed to be beneficial in fasting or high-fat diet induced inflammation [68,69].…”

Potential ghrelin-mediated benefits and risks of hydrogen water

“…Ghrelin administration has shown protective activity in rodent models of non-alcoholic fatty liver disease, liver damage induced by carbon tetrahydrochloride or acetaminophen, and hepatic ischemia-reperfusion [106][107][108][109][110]. Since TNF-alpha is a key mediator of hepatic inflammation in many syndromes, ghrelin-mediated suppression of this cytokines seems likely to play a role in these benefits.…”