Biology subjects

Bombassaro, B.

Publications and source records attributed to Bombassaro, B..

2 recordsLinked to original sources

bioRxiv2024

Sympathetic neuron-derived NPY protects from obesity by sustaining the mural progenitors of thermogenic adipocytes.

Neuropeptide Y (NPY) is secreted by sympathetic nerves1,2, but its direct impact on thermogenic adipocytes is unknown. Here we uncover the mechanism by which peripheral NPY protects from obesity. Our imaging of cleared murine brown and white adipose tissue (BAT and WAT) established that NPY+ sympathetic axons are only a minority that mostly maps to the peri-vasculature; our analysis of single-cell RNA-sequencing datasets identifies mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains mural cells, which are known to be a source of beige cells in both BAT and WAT3-5 and that NPY facilitates the differentiation to thermogenic adipocytes. We found that diet-induced-obesity leads to neuropathy of NPY+ axons and concomitant depletion of the mural cell pool of beige fat progenitors. This defect is replicated in conditional knockout (cKO) mice with NPY specifically abrogated from sympathetic neurons. These cKO mice have whitened BAT with reduced thermogenic ability and lower energy expenditure even before the onset of obesity; they develop adult-onset obesity on a regular chow diet and are more susceptible to diet induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by the sympathetic nerves has the opposite effect on body weight homeostasis by sustaining the proliferation of the mural cell progenitors of thermogenic adipocytes.

physiology↗

bioRxiv2022

A Diabetic Mice Model For Studying Skin Wound Healing

Advances in wound treatment depend on the availability of suitable animal models. All animal models try to reflect human wound healing problems. For acute wounds, it is easier to obtain adequate animal models, however, for chronic wounds such as those found in individuals with diabetic foot ulcer, approximations of the clinical picture become a challenge. Nowadays, the key points of wound healing processes are better understood, and therefore, therapeutic strategies can be developed to manipulate wound repair. Research efforts involves the development of therapies to aid in the treatment of impaired wound healing and, to improving normal wound healing to drive a process close to regenerative. To achieve a better animal model that is more appropriate for studying wound healing, six-week- old male C57BL/6 mice were separated into groups fed a Chow and High-Fat Diet for 0.5, 3, and 6 months, when part of the animals were induced to diabetes by streptozotocin. Then, mice were submitted to metabolic, molecular, and morphological analyses. We show that this model results in a severe metabolic phenotype with insulin resistance, reduced insulin expression, and glucose intolerance associated with obesity and, more importantly, skin changes. Furthermore, the skin phenotype, both structurally and transcriptionally, overlapped with conditions found in elderly patients with DM that reproduce the phenotype of most patients who develop diabetic foot ulcers.

physiology↗