Distinct sympathetic projections to brown fat regulate thermogenesis and glucose tolerance

Area of Science:

• Neuroscience
• Metabolic Research
• Adipose Tissue Biology

Background:

• Brown adipose tissue (BAT) is crucial for thermoregulation and glucose metabolism.
• Coordination between BAT's thermogenic and metabolic functions is not fully understood.
• Distinct sympathetic circuits may govern these separate functions.

Purpose of the Study:

• To identify and characterize distinct sympathetic neuron subpopulations controlling brown adipose tissue (BAT) functions.
• To elucidate the specific roles of parenchymal and vascular projections in BAT activity.
• To explain the dissociation between thermogenic and glycemic effects of BAT activation.

Main Methods:

• Development of a toolkit for targeted chemogenetic activation of specific sympathetic neuron projections to iBAT.
• Utilizing single-cell transcriptomics coupled with retrograde tracing from iBAT to the stellate ganglion.
• Functional assessment of neuronal subclass activation on BAT blood flow, thermogenesis, and glucose metabolism in mice.

Main Results:

• Stimulation of parenchymal projections increased iBAT blood flow and thermogenesis without affecting circulating glucose.
• Activation of vascular projections improved glucose tolerance but did not alter iBAT blood flow or thermogenesis.
• Identified distinct functional roles for sympathetic neuron subclasses innervating iBAT.

Conclusions:

• Sympathetic neurons in the stellate ganglion exhibit functional specialization in controlling iBAT.
• Parenchymal projections are primarily involved in thermogenesis and blood flow regulation.
• Vascular projections play a key role in modulating glucose tolerance, independent of thermogenesis.