With rising rates of obesity and related metabolic diseases being reported worldwide, researchers have struggled to understand the functional state of the body’s adipose tissue in relation to overall energy balance. new temper nature The study investigates the sensory innervation of fat cells within the subcutaneous fat deposits, and determines the anatomical and functional implications of interference with sensory nerves in these tissues.
Stady: The role of somatosensory innervation of adipose tissue. Image credit: SciePro / Shutterstock.com
an introduction
In mammals, adipose tissue is fueled by sympathetic and sensory nerves. The sympathetic nerves carry signals from the sympathetic nervous system via beta-adrenergic receptors to regulate fat metabolism and heat production from fat. These nerves are actively involved in the metabolism of beige and brown fats.
Fat cells also transmit sensory signals that enter the central nervous system through the dorsal root ganglia (DRG) of the spinal cord. Previous studies using the herpes virus have clarified the pathway of these nerves. However, their functional role remains unclear, as cutting or chemically disrupting these nerves did not produce any significant changes in hamster experiments.
The methods used in the above studies are considered flawed, as they are not able to selectively target the somatosensory fibers. For this reason, researchers in the current study sought to develop better methods using imaging, molecular, and circuit selectivity tools.
The HYBRID visualization tool, for example, uses mass fluorescence for large tissues, which is a prerequisite for visualizing the long peripheral axis of the mouse DRG. This approach will allow researchers to visualize the entire sensory nerve from DRG fat cells to fat cells.
In addition to this tool, the researchers in the current study injected recombinant adeno-associated virus (AAV) expressing a fluorescent protein into individual DRGs at the thoracolumbar level, subsequently leaving the sympathetic ganglia through delicate microsurgery. This will display all the fibers protruding from the two selected sensory ganglia.
In the current study, the researchers used a white adipose tissue (WAT) pad in the thigh, which consists of metabolically active beige fat, as it is known to have important functions in the physiology of mice.
Results
Using HYBRID imaging and optical paper, it was observed that the complete projection length of DRG neurons from the cell body to the thigh fat pad was 1.2 cm. This demonstrated direct innervation of the sebaceous pad by thoracolumbar DRGs.
The researchers removed any confusion between the sensory fibers of the skin of the thigh and those in the fat pad by using two-color labels with the CTB subunit. The fat sensory fibers were of two types, one forming larger bundles that traveled along the blood vessels to the tissues and the other the parenchymal type that showed sensory nerve endings near the fat cells.
Approximately 40% of the parenchymal fibers were positive for tyrosine hydroxylase (TH), which was previously considered a selective marker for sympathetic fibers. This observation indicated the potential for errors in previous studies that relied on the discovery of TH to determine the sympathetic innervation of adipose tissue.
Job roles
Because sensory fibers use many different neurotransmitters, the researchers used genetic engineering to study specific neurons with an eye toward their projections. To this end, AAV9 was used because it is safer and better for demonstrating long-term functional changes, rather than pseudoviruses and herpes simplex, both of which are toxic.
This approach is known as ROOT (ROOT). The superiority of this approach is due to its high retrograde efficiency and low rate of off-target expression in DRGs on the opposite side or the liver. Using ROOT, the researchers resected only sensory nerves in the fat pad, which subsequently resulted in a 40% reduction in fat-projecting neurons in the treated DRGs.
The sensory nerve endings in the skin with fibers that travel with those in the sebaceous pad remained intact. This confirmed that the scientists had achieved a specific loss-of-function model for the somatosensory fibers that innervate lipids.
Genetic studies showed that somatosensory ablation increased thermogenesis in the fat pad, as well as again The fat is similar to that of beige or brown fat. This is an unusual combination of lipid oxidation and lipogenesis, which makes heat production possible, even under cold conditions or following beta-adrenergic signaling.
The observed thermogenesis was mediated by the activity of hormone-sensitive lipase (HSL), with a higher number of multicellular beige adipocytes on the blister side.
Loss of sympathetic innervation in these animals reduced this response. Thus, sympathetic function is required for the genetic response to sensory innervation.
With double excision, the fat mass increases on the depleted side, which is different from the contraction that usually occurs with increased thermogenesis. This indicates that sensory fibers are also involved in coordinating lipogenesis and thermogenesis.
When the fat pads on both sides were deprived of their sensory innervation, the animals maintained a constant body weight, normal food intake, and predictable responses to temperature. No obvious changes in sympathetic tone were observed.
The largest change was in basal body temperature, which increased and as a consequence was associated with higher thermogenesis. At 22 °C, the temperature stabilized, indicating that the central thermostat mechanisms remained intact.
When tested with a high-fat diet, the excised mice showed better glucose tolerance compared to controls; However, the body weight changed slightly. This change supports white lipogenesis in response to sensory ablation of adipose tissue, with a protective effect on glucose metabolism.
Ramifications
The current study adds new information about adipose tissue regulation to the available knowledge. Moreover, the results of the study showed that in addition to slow generalized signals from fat cells through adipocyte hormones, fat tissue also sends sensory signals via somatosensory nerves to the brain. This indicates the possibility of rapidly sensing changes in specific locations of fat deposits in the body.
Study results also show that DRGs suppress sympathetic tone localized in adipose tissue, such as baroreceptor-mediated vagal blood pressure regulation. This provides new insights into internal perception, the process by which the body maintains the multiplicity of internal processes and changes that occur in each moment.
The mechanisms linking sensory and sympathetic signals remain unknown. Further research will be required to determine the functions of the different DRG subtypes that innervate adipose tissue, as well as the nature of the signaling itself.