He, Z.-h. | Search bioRxiv

bioRxiv2019

α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation

Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in vivo. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate -ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically-derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

molecular biology↗

bioRxiv2019

Infection of Borrelia burgdorferi sensu lato of small mammals in Yunnan Province, China

BackgroundLyme disease is caused by Borrelia burgdorferisensulato (BBSL) which is usually found in wild and domestic mammals worldwide. Human cases of B. burgdorferi infections have been identified in China, but little direct surveillance of potential rodent reservoirs has been performed in Yunnan Province, Southwestern China. Yunnan Province is a tropical area with a diverse topographic range and sustains a high biodiversity of small mammals that could potentially play an important role in the transmission of a variety of B. burgdorferigenospecies.\n\nMethods3659 small mammals were captured in 159 sample siteslocated 23 countries inYunnan Province and screened for BBSL infection by nested PCR based on 5S-23S rRNA intergenic spacer gene of BBSL.Univariate and multivariate forward stepwise logistic regression analysis was used to access the association between infections and related risk factors.\n\nResultsInfection with BBSL was confirmed in 3.99%(146/3659) of small mammals. Significant differences in prevalence rates of BBSL were observed at varying landscape types and altitudes.Small mammals in forested areas had higher prevalence rates than other landscape types as did small mammals found at altitudes greater than 2500 meters. The 5S-23S rRNA intergenic spacergene revealed that there were 5 genotype of BBSL, including B. afzelii, B. burgdorferisensustricto, B.japonica, B.gariniiand B.valaisiana, which demonstrate the genetic diversity and regional distribution.\n\nConclusionsThere exists a wide distribution and genetic diversity of endemic BBSL in Southwestern China, warranting further investigations and monitoring of clinical disease in individuals presenting with symptoms of Lyme disease in these areas.\n\nAuthor summaryLyme disease is caused by Borrelia burgdorferi sensu lato (BBSL) which is usually found in wild and domestic mammals worldwide. Human cases of Borrelia burgdorferi sensu lato infections have been identified in China, but little direct surveillance of potential rodent reservoirs has been performed in Southwestern China. This study documents potential small mammal reservoir hosts collected from a large of sample sites from different landscape types and altitudes, with PCR and sequencing identifying the wide distribution and genetic diversity of endemic Borrelia burgdorferi sensu lato in Southwestern China. This was the first report that B. japonica was detected in Apodemus draco and Niviventer excelsior in China. This study adds to body of literature on Borrelia burgdorferi sensu lato in China. This work will provide insight regarding small mammals to target for surveillance and we access the association between gender, developmental stage of rodents, environmental landscape and altitude to better prevent human exposure.

epidemiology↗