Effect of Lingguizhugan decoction in activating fat mobilization in obesity

To observe the effects of Lingguizhugan decoction on obesity and investigate its preliminary mechanism in activating fat mobilization based on gut microbiota. In this prospective one-armed clinical research, we analyzed the data of 32 obese patients with Yang deficiency and phlegm-dampness syndrome treated by Lingguizhugan decoction combined with lifestyle intervention for 2 months. The anthropometric data, body composition, metabolic data, traditional Chinese medicine (TCM) syndrome scores, fecal 16S rDNA, core temperature, and visceral fat fractions of patients were analyzed. Animal experiments were conducted for further verification: ob/ob mice and pseudo-germ-free ob/ob mice (ABX) were given Lingguizhugan decoction by gavage for 2 months. The body mass, core temperature (rectum), respiratory exchange ratio (RER), micro-positron emission tomography/computed tomography (micro-PET/CT) results, and uncoupling protein 1 (UCP1) expression (including gene, protein, and immunohistochemistry staining results) in inguinal adipose tissue of mice were evaluated. The clinical effective rates of TCM and Western medicine were 96.87% and 93.75%, respectively. Compared with those before treatment, the body mass index (BMI), body fat ratio (BFR), waist-to-hip ratio, TCM syndrome scores, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPPG), glycosylated hemoglobin A1C (GHbA1c), and blood uric acid (UA) significantly decreased after treatment. Moreover, we randomly selected five patients to investigate their core temperature and visceral fat fractions. Compared with healthy volunteers, the five patients had higher core temperature. According to the 1.5 T magnetic resonance imaging (MRI) results, the fat fractions of the liver, pancreas, greater omentum, and subcutaneous abdominal wall were notably decreased after treatment. Fecal 16S rDNA principal component analysis and partial least squares discriminant analysis showed that the biodiversity and species abundance of gut microbiota were significantly different between pre- and post-treatment. The relative abundance of Bacteroidetes was remarkably elevated and that of Firmicutes was notably reduced by Lingguizhugan decoction. The animal experiments showed that the weight of ob/ob mice decreased significantly by gavage of Lingguizhugan decoction for 2 months. Compared with the model group, the Lingguizhugan group showed increased core temperature (rectum) and decreased RER. Micro-PET/CT showed that 18F-2-deoxyglucose-6-phosphate (18F-FDG) was enriched obviously and the SUV index was increased in the Lingguizhugan group. However, after eliminating the gut microbiota in the ABX group, the weight loss, core temperature, 18F-FDG enrichment, and SUV index decreased, and RER was similar to that in the model group despite simultaneous treatment with Lingguizhugan decoction. According to the gene, protein, and immunohistochemistry results UCP1 expression in inguinal adipose tissue of mice in the Lingguizhugan decoction group was significantly higher than that in the model group. However, UCP1 expression in the ABX group was downregulated after eliminating the gut microbiota. Lingguizhugan decoction combined with lifestyle intervention effectively improved the BMI, BFR, glucolipid metabolism, and TCM syndrome scores of obese patients with Yang deficiency and phlegm-dampness syndrome. We infer that the mechanism of Lingguizhugan decoction in promoting fat mobilization may lie in the browning of white adipose tissue (WAT) triggered by gut microbiota. Further animal experiments indicated that Lingguizhugan decoction promoted the browning of WAT and activation of fat mobilization by gut microbiota.