Sensory denervation of inguinal white fat modifies sympathetic outflow to white and brown fat in Siberian hamsters.

White adipose tissue (WAT) and brown adipose tissue (BAT) have sympathetic nervous system (SNS) and sensory innervations. Previous studies from our laboratory revealed central neuroanatomical evidence of WAT sensory and BAT SNS crosstalk with double labeling of inguinal WAT (IWAT) sensory and interscapular BAT (IBAT) SNS neurons. We previously demonstrated that WAT lipolysis increases IBAT temperature, but this effect is absent when IWAT afferents are surgically denervated, which severs both sensory and SNS nerves. It is possible that WAT sensory feedback can regulate SNS drive to itself and other WAT and BAT depots, and thus contribute to the existence of differential SNS outflow to fat during different energy challenges. Here we selectively denervated IWAT sensory nerves in Siberian hamsters using capsaicin and measured norepinephrine turnover (NETO) i.e., SNS drive to WAT and BAT depots, IBAT uncoupling protein 1 (UCP1) expression, body mass, fat mass, blood glucose, and food consumed after a 24-h cold exposure. IWAT sensory denervation decreased both IWAT and IBAT NETO and IBAT UCP1 expression. IWAT sensory denervation, however, increased mesenteric WAT (MWAT) NETO after the 24-h cold exposure and did not modify epididymal WAT (EWAT) and retroperitoneal WAT (RWAT) NETO compared with respective controls. Body mass, fat mass, blood glucose, and food consumed were unchanged across groups. RWAT and EWAT mass decreased in capsaicin-injected hamsters, but did not in the vehicle hamsters. These results functionally demonstrate the existence of IWAT sensory and IBAT SNS crosstalk and that a disruption in this sensory-SNS feedback mechanism modifies SNS drive to IWAT, IBAT, and MWAT, but not EWAT and RWAT.

Nguyen NLT ，Xue B ，Bartness TJ 《-》

Separate and shared sympathetic outflow to white and brown fat coordinately regulates thermoregulation and beige adipocyte recruitment.

White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16-24 h and measured core and fat temperatures and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT across the neuroaxis. However, there was a greater percentage of singly labeled IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The hindbrain had ~30-40% of doubly labeled neurons while the forebrain had ~25% suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons. Hamsters with IBAT SNS denervation maintained core body temperature during acute cold challenge and had increased beige adipocyte formation in IWAT. They also had increased IWAT NETO, temperature, and UCP1 expression compared with intact hamsters. These data provide strong neuroanatomical and functional evidence of WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation.

Nguyen NL ，Barr CL ，Ryu V ，Cao Q ，Xue B ，Bartness TJ ... -  《-》

Bidirectional crosstalk between the sensory and sympathetic motor systems innervating brown and white adipose tissue in male Siberian hamsters.

The brain networks connected to the sympathetic motor and sensory innervations of brown (BAT) and white (WAT) adipose tissues were originally described using two transneuronally transported viruses: the retrogradely transported pseudorabies virus (PRV), and the anterogradely transported H129 strain of herpes simplex virus-1 (HSV-1 H129). Further complexity was added to this network organization when combined injections of PRV and HSV-1 H129 into either BAT or WAT of the same animal generated sets of coinfected neurons in the brain, spinal cord, and sympathetic and dorsal root ganglia. These neurons are well positioned to act as sensorimotor links in the feedback circuits that control each fat pad. We have now determined the extent of sensorimotor crosstalk between interscapular BAT (IBAT) and inguinal WAT (IWAT). PRV152 and HSV-1 H129 were each injected into IBAT or IWAT of the same animal: H129 into IBAT and PRV152 into IWAT. The reverse configuration was applied in a different set of animals. We found single-labeled neurons together with H129+PRV152 coinfected neurons in multiple brain sites, with lesser numbers in the sympathetic and dorsal root ganglia that innervate IBAT and IWAT. We propose that these coinfected neurons mediate sensory-sympathetic motor crosstalk between IBAT and IWAT. Comparing the relative numbers of coinfected neurons between the two injection configurations showed a bias toward IBAT-sensory and IWAT-sympathetic motor feedback loops. These coinfected neurons provide a neuroanatomical framework for functional interactions between IBAT thermogenesis and IWAT lipolysis that occurs with cold exposure, food restriction/deprivation, exercise, and more generally with alterations in adiposity.

Ryu V ，Watts AG ，Xue B ，Bartness TJ ... -  《-》

Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation.

Brito MN ，Brito NA ，Baro DJ ，Song CK ，Bartness TJ ... -  《ENDOCRINOLOGY》

Sensory or sympathetic white adipose tissue denervation differentially affects depot growth and cellularity.

Shi H ，Song CK ，Giordano A ，Cinti S ，Bartness TJ ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY》