Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent-hot (warm) herbs to demonstrate their natures.
Adipose Tissue, Brown ; drug effects ; physiology ; Animals ; Capsaicin ; analogs & derivatives ; pharmacology ; Energy Metabolism ; Ganglia, Spinal ; cytology ; HEK293 Cells ; Humans ; Mice ; Neurons ; drug effects ; physiology ; Plants, Medicinal ; chemistry ; TRPV Cation Channels ; physiology ; Temperature ; Thermogenesis

OBJECTIVETo measure simultaneously the time course for the circadian rhythm of brown adipose tissue(BAT) thermogenesis and core temperature, and analyzing their temporal relationship.

METHODSThe circadian rhythm of core temperature (Tc), BAT temperature (T(BAT)), axillary temperature (Tax) and motor activity were simultaneously measured by telemetry in adult male Sprague-Dawley rats at an ambient temperature of 22 degrees C during a 12-h light:12-h dark photoperiod (lights on at 06:00 h and lights off at 18:00 h).

RESULTS(1) T(BAT) was 0.67 degrees C lower than Tc group under the light phase, but it was similar to that Tc during the dark phase. The rate of increase in T(BAT) was higher than corresponding increases in Tc at the start of transition from the light to dark phase, and increase in T(BAT) commenced approximately 8 min before Tc increases. Whereas at the start of transition from the dark to light phase, decrease in T(BAT) commenced approximately 4 min before Tc decreases. (2) The amplitude of the circadian Tax rhythm was similar to that of Tc. During either the light phase or dark phase, Tax was lower than simultaneous measurement of Tc. (3) Increases in behavioral activity commenced before increases in T(BAT) and Tc at the start of transition from the light to dark phase.

CONCLUSIONBAT thermogenesis contributes to increase in core temperature during the dark phase, indicating that circadian changes of BAT thermogenesis does indeed play significant role in the overall maintenance of the circadian rhythm of core temperature.

Adipose Tissue, Brown ; metabolism ; physiology ; Animals ; Body Temperature ; physiology ; Circadian Rhythm ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Telemetry ; methods ; Thermogenesis ; physiology