Parkin depletion prevents the age-related alterations in the FGF21 system and the decline in white adipose tissue thermogenic function in mice.

Parkin is an ubiquitin-E3 ligase that is involved in cellular mitophagy and was recently shown to contribute to controlling adipose tissue thermogenic plasticity. We found that Parkin expression is induced in brown (BAT) and white (WAT) adipose tissues of aged mice. We determined the potential role of Parkin in the aging-associated decline in the thermogenic capacity of adipose tissues by analyzing subcutaneous WAT, interscapular BAT, and systemic metabolic and physiological parameters in young (5 month-old) and aged (16 month-old) mice with targeted invalidation of the Parkin (Park2) gene, and their wild-type littermates. Our data indicate that suppression of Parkin prevented adipose accretion, increased energy expenditure and improved the systemic metabolic derangements, such as insulin resistance, seen in aged mice. This was associated with maintenance of browning and reduction of the age-associated induction of inflammation in subcutaneous WAT. BAT in aged mice was much less affected by Parkin gene invalidation. Such protection was associated with a dramatic prevention of the age-associated induction of fibroblast growth factor-21 (FGF21) levels in aged Parkin-invalidated mice. This was associated with a parallel reduction in FGF21 gene expression in adipose tissues and liver in aged Parkin-invalidated mice. Additionally, Parkin invalidation prevented the protein down-regulation of ß-Klotho (a key co-receptor mediating FGF21 responsiveness in tissues) in aged adipose tissues. We conclude that Parkin down-regulation leads to improved systemic metabolism in aged mice, in association with maintenance of adipose tissue browning and FGF21 system functionality.

Occurrence and Genetic Diversity of Protist Parasites in Captive Non-Human Primates, Zookeepers, and Free-Living Sympatric Rats in the Córdoba Zoo Conservation Centre, Southern Spain.

Little information is currently available on the epidemiology of parasitic and commensal protist species in captive non-human primates (NHP) and their zoonotic potential. This study investigates the occurrence, molecular diversity, and potential transmission dynamics of parasitic and commensal protist species in a zoological garden in southern Spain. The prevalence and genotypes of the main enteric protist species were investigated in faecal samples from NHP (n = 51), zookeepers (n = 19) and free-living rats (n = 64) by molecular (PCR and sequencing) methods between 2018 and 2019. The presence of Leishmania spp. was also investigated in tissues from sympatric rats using PCR. Blastocystis sp. (45.1%), Entamoeba dispar (27.5%), Giardia duodenalis (21.6%), Balantioides coli (3.9%), and Enterocytozoon bieneusi (2.0%) (but not Troglodytella spp.) were detected in NHP. Giardia duodenalis (10.5%) and Blastocystis sp. (10.5%) were identified in zookeepers, while Cryptosporidium spp. (45.3%), G. duodenalis (14.1%), and Blastocystis sp. (6.25%) (but not Leishmania spp.) were detected in rats. Blastocystis ST1, ST3, and ST8 and G. duodenalis sub-assemblage AII were identified in NHP, and Blastocystis ST1 in zookeepers. Giardia duodenalis isolates failed to be genotyped in human samples. In rats, four Cryptosporidium (C. muris, C. ratti, and rat genotypes IV and V), one G. duodenalis (assemblage G), and three Blastocystis (ST4) genetic variants were detected. Our results indicate high exposure of NHP to zoonotic protist species. Zoonotic transmission of Blastocysts ST1 was highly suspected between captive NHP and zookeepers.