Bifidobacterium adolescentis Alleviates Liver Steatosis and Steatohepatitis by Increasing Fibroblast Growth Factor 21 Sensitivity.

The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of Bifidobacterium adolescentis (B. adolescentis), a species of Bifidobacterium that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether B. adolescentis treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with B. adolescentis for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, B. adolescentis supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that B. adolescentis supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and ß-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that B. adolescentis supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that B. adolescentis supplementation could alleviate NAFLD by increasing FGF21 sensitivity.

Osteocalcin attenuates high fat diet-induced impairment of endothelium-dependent relaxation through Akt/eNOS-dependent pathway.

BACKGROUND: Recent studies have demonstrated a protective effect of osteocalcin (OCN) on glucose homeostasis and metabolic syndrome. However, its role in vascular function remains unknown. This study investigated the contribution of OCN to the pathogenesis of endothelial dysfunction in the thoracic aorta of apolipoprotein E-deficient (ApoE-KO) mice. METHODS: Eight-week-old ApoE-KO mice were given chow or high fat diet (HFD) for 12 weeks with or without daily intraperitoneal injection of OCN. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT),measurement of serum lipid profiles and blood pressure were carried out. Endothelium-dependent relaxation (EDR) was measured by wire myography. Human umbilical vein endothelial cells (HUVECs) were used to study the role of OCN on eNOS levels in vitro. PI3K inhibitor (LY294002) and Akt inhibitor V were used ex-vivo to determine whether PI3K/Akt/eNOS contributes to the beneficial effect of OCN for the vascular or not. RESULTS: Daily injections of OCN can significantly improve lipid metabolism, glucose tolerance and insulin sensitivity in ApoE-KO mice. In ApoE-KO mice fed with HFD, the OCN-treated mice displayed an improved acetylcholine-stimulated EDR compared to the vehicle-treated group. In addition, compared to vehicle-treated HUVECs, OCN-treated HUVECs displayed increased activation of the Akt-eNOS signaling pathway, as evidenced by significantly higher levels of phosphorylated Akt and eNOS. Furthermore, a similar beneficial effect of OCN on thoracic aorta was observed using ex vivo organ culture of isolated mouse aortic segment. However, this effect was attenuated upon co-incubation with PI3K inhibitor or Akt inhibitor V. CONCLUSIONS: Our study demonstrates that OCN has an endothelial-protective effect in atherosclerosis through mediating the PI3K/Akt/eNOS signaling pathway.

[Prognosis and treatment of sudden sensorineural hearing loss with total and severe all frequency hearing loss].

OBJECTIVE: To evaluate the treatment and prognosis of sudden sensorineural hearing loss (SSHL) with total and severe all frequency hearing loss. METHODS: Sixty-two patients diagnosed as SSHL (0.25, 0.5, 1, 2, 4 kHz pure tone average > or = 56 dB) were studied from January 2003 to October 2006, in which 18 of them were treated with Xueshuantong (Panax notoginseng saponins) while 19 of them treated with steroid and Xueshuantong, and 25 of them treated with steroid, DF-521 and Xueshuantong. RESULTS: The hearing improvement rate of the patients treated with Xueshuantong was 22.2% (4/18) while the patients treated with steroid and Xueshuantong was 57.9% (11/19) and the patients treated with steroid, DF-521 and Xueshuantong was 68.0% (17/25). The good improvement rate of the patients treated with Xueshuantong was 5.6% (1/18) while the patients treated with steroid and Xueshuantong was 36.8% (7/19) and the patients treated with steroid, DF-521 and Xueshuantong was 60.0% (15/25). Over hearing improvement was significantly better in patients treated with steroid, defibrinogenation and Xueshuantong than in those treated with Xueshuantong only (P < 0.05). The patients of total hearing loss had a significantly higher vertigo rate and worse therapy effect. CONCLUSIONS: The combined therapy include high-dose corticosteroids and defibrinogenation therapy is effective for the patients with total deafness and severe all frequency hearing loss. The prognosis of patients with total hearing loss was poor.