OBJECTIVES: To explore the mechanisms of moxibustion in treating obese mice through its regulatory effects on mitochondrial brown adipose tissue uncoupling protein-1 (UCP1), PR domain-containing protein 16 (Prdm16), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in abdominal adipose tissue, and the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling pathway in the hypothalamus of obese mice.
METHODS: C57BL/6J mice were randomly divided into the control group, model group, moxibustion group, and sham control group, with 10 mice in each group. An obese mouse model was established by feeding a high-fat diet. Moxibustion was applied mildly at a distance of 3-5 cm from the"Zhongwan"(CV12) with a temperature maintained at (46±1)℃ in the moxibustion group. In the sham control group, moxibustion was applied at a distance of 8-10 cm from CV12 with a temperature maintained at (38±1)℃. Changes in body weight and food intake were observed before and after treatment. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum triglycerides (TG), total cholesterol (TC), and hypothalamic cAMP. The mass of abdominal white adipose tissue (WAT) was assessed. Histopathological changes in adipose tissue were observed using hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative PCR and Western blot were employed to detect the mRNA and protein expression of UCP1, Prdm16, and PGC-1α in abdominal adipose tissue, as well as the expression of PKA and CREB in the hypothalamus.
RESULTS: Compared with the control group, the model group showed increased body weight, food intake, serum TC and TG levels (<0.01), as well as increased abdominal WAT mass (<0.01), and significantly enlarged adipocyte volume in abdominal adipose tissue. Mice in the model group showed decreased mRNA and protein expression of UCP1, Prdm16, and PGC-1α in abdominal adipose tissue, as well as decreased mRNA and protein expression of PKA and CREB in the hypothalamus (<0.01), along with decreased levels of hypothalamic cAMP (<0.01). Compared with the model group and sham control group, the moxibustion group showed decreased body weight and food intake (<0.01,<0.05), decreased serum TC and TG levels, and abdominal WAT mass (<0.01), along with reduced adipocyte diameter in abdominal adipose tissue. Moreover, compared with the model group and sham control group, the moxibustion group showed increased mRNA and protein expression of UCP1, Prdm16, and PGC-1α in abdominal adipose tissue, and the mRNA and protein expression of PKA and CREB in the hypothalamus (<0.01), as well as increased levels of hypothalamic cAMP (<0.01). P P P P P P P P P
CONCLUSIONS: Moxibustion can enhance the mRNA and protein expression of UCP1, Prdm16, and PGC-1α in WAT of obese mice, improving obesity and lipid metabolism. Its mechanism may involve the regulation of the hypothalamic cAMP/PKA/CREB signaling pathway.