Fibroblast growth factor 21 (FGF21) therapy attenuates left ventricular dysfunction and metabolic disturbance by improving FGF21 sensitivity, cardiac mitochondrial redox homoeostasis and structural changes in pre-diabetic rats.

AIMS: Fibroblast growth factor 21 (FGF21) acts as a metabolic regulator and exerts cardioprotective effects. However, the effects of long-term FGF21 administration on the heart under the FGF21-resistant condition in obese, insulin-resistant rats have not been investigated. We hypothesized that long-term FGF21 administration reduces FGF21 resistance and insulin resistance and attenuates cardiac dysfunction in obese, insulin-resistant rats. METHODS: Eighteen rats were fed on either a normal diet (n = 6) or a high-fat diet (HFD; n = 12) for 12 weeks. Then, rats in the HFD group were divided into two subgroups (n = 6 per subgroup) and received either the vehicle (HFV) or recombinant human FGF21 (rhFGF21, 0.1 mg kg(-1)  day(-1) ; HFF) injected intraperitoneally for 28 days. The metabolic parameters, inflammation, malondialdehyde (MDA), heart rate variability (HRV), left ventricular (LV) function, cardiac mitochondrial redox homoeostasis, cardiac mitochondrial fatty acid ß-oxidation (FAO) and anti-apoptotic signalling pathways were determined. RESULTS: HFV rats had increased dyslipidaemia, insulin resistance, plasma FGF21 levels, TNF-α, adiponectin and MDA, depressed HRV, and impaired LV and mitochondrial function. HFV rats also had decreased cardiac Bcl-2, cardiac PGC-1α and CPT-1 protein expression. However, FGF21 restored metabolic parameters, decreased TNF-α and MDA, increased serum adiponectin, and improved HRV, cardiac mitochondrial and LV function in HFF rats. Moreover, HFF rats had increased cardiac Bcl-2, cardiac PGC-1α and CPT-1 protein expression. CONCLUSION: Long-term FGF21 therapy attenuates FGF21 resistance and insulin resistance and exerts cardioprotection by improving cardiometabolic regulation via activating anti-apoptotic and cardiac mitochondrial FAO signalling pathways in obese, insulin-resistant rats.

Hepatitis B virus infection in non-human primates.

Hepatitis B viruses (HBVs) represent a serious public health problem affecting 350 to 400 million HBV carriers worldwide. The virus does not exclusively infect humans, but can also be found in non-human primates as in the families Hominidae (chimpanzee, gorilla, orangutan) and Hylobatidae (gibbon), which are distributed over Africa (chimpanzee and gorilla) and Southeast Asia (orangutan and gibbon), the endemic areas of human HBV. The prevalence of asymptomatic HBV carriers reaches in gibbons 23-33% and in orangutans 15%. The genome organization of non-human primate HBVs is nearly identical to that of human HBVs. Because of this close similarity, the question of cross-transmission of HBV between species has arisen. There are many data on cross-transmission of human HBVs to the non-human primates. However, a cross-transmission of HBVs from non-human primates to humans has not been reported yet. Using more advanced diagnostic methods, the non-human primates have increasingly been identified as a reservoir of several viruses such as lymphocryptoviruses, Cercopithecine herpesvirus 1 (CeHV-1), Simian immunodeficiency virus (SIV), Simian foamy virus (SFV), and HBVs. Thus veterinarians, zookeepers, or people in close contact with non-human primates may potentially become infected with those viruses causing severe diseases. Enhanced awareness of prevalence, genetic relatedness and evolution of non-human primate HBVs will help prevent further spread and cross-transmission of these viruses between humans and non-human primates.

Molecular characterisation of the hepatitis A virus circulating in the 2001-2005 outbreaks in Thailand.

In a recent study of hepatitis A virus (HAV) in Thailand, viral isolates recovered during several outbreaks of infection that occurred between 2001 and 2005 were genotyped and subjected to phylogenetic analysis. Anti-HAV IgM was detected, by ELISA, in many of the 283 serum samples that were collected from the provinces of Suphanburi, Songkhla, Chiangrai and Lampang: 40 (48.2% of those investigated), 38 (47.5%), 25 (41.0%) and 32 (54.2%), respectively. The HAV RNA in the positive samples was reverse transcribed and amplified, using a nested PCR focussed on the VP1-2A region, before the nucleotides of the VP1-2A region of each HAV-RNA-positive sample were sequenced. All the isolates investigated clustered in subgenotype IA and, hence, are closely related to the strains previously investigated in Thailand. When the genome of one sample from an outbreak in Lampang (LP014) was fully sequenced, the results of genome comparison and phylogenetic analysis again indicated subgenotype 1A, which appears to be the predominant form of HAV circulating throughout Thailand.