Notoginsenoside Fe suppresses diet induced obesity and activates paraventricular hypothalamic neurons

Abstract

Obesity has become a major public health challenge worldwide. Energy imbalance between calorie acquisition and consumption is the fundamental cause of obesity. Notoginsenoside Fe is a naturally occurring compound in Panax notoginseng, a herb used in the treatment of cardiovascular diseases in traditional Chinese medicine. Here, we evaluated the effect of notoginsenoside Fe on obesity development induced by high-fat diet in C57BL/6 mice. Our results demonstrated that notoginsenoside Fe decreased food intake and body weight, as well as protected liver structure integrity and normal function. Metabolic cage analysis showed that notoginsenoside Fe also promoted resting metabolic rate. In addition, intracerebroventricular (i.c.v) injection of notoginsenoside Fe induced C-Fos expression in the paraventricular nucleus (PVH) but not the arcuate nucleus (ARC) of the hypothalamus. These results suggest that Fe may reduce body weight through the activation of energy-sensing neurons in the hypothalamus.

Fig. 1. Notoginsenoside Fe ameliorates diet-induced obesity. (A) Chemical structure of notoginsenoside Fe. (B) Body weight. (C) Body weight changes. (D) Images of mice body type. (E) Food intake amount. (F) Fasting blood glucose. (G) Intraperitoneal glucose tolerance test. The blood glucose levels at the indicated intervals (15, 30, 60, 90, 120 min) after glucose injection intraperitoneally. All data were analyzed by one-way analysis of variance with Dunnett test or un-paired Student's t-test. N = 5, *P < 0.05, **P < 0.01, ***P < 0.001 vs. HF group; ^#P < 0.05, ^###P < 0.001 vs. chow. Notoginsenoside Fe was expressed as Fe.

Fig. 2. Notoginsenoside Fe treatment ameliorates hepatic steatosis in diet-induced obese mice. (A) Liver section morphology stained with H&E. (B) TC and TG contents in the liver. (C and D) The serum ALT and AST levels. Comparisons among three groups or two groups were analyzed by one-way analysis of variance with Dunnett test or un-paired Student's t-test. N = 5, *P < 0.05 vs. HF group; ^#P < 0.05, ^#P < 0.05, ^###P < 0.001 vs. chow. Notoginsenoside Fe was expressed as Fe.

Fig. 3. Notoginsenoside Fe treatment reduces fat mass in diet-induced obese mice. (A) WAT section morphology stained with H&E. (B and C) The percentages of fat and lean compared with body weight. (D) The mRNA expression level of genes related to glucose and lipid metabolism. All data were analyzed by one-way analysis of variance with Dunnett test or un-paired Student's t-test, respectively. N = 5, *P < 0.05, ***P < 0.001 vs. HF group; ^###P < 0.001 vs. chow. Notoginsenoside Fe was expressed as Fe.

Fig. 4. Effect of notoginsenoside Fe on metabolic measures. (A–F) VO₂, VCO₂, and RER values. The data represented as average of three dark and three light cycles, and were analyzed by un-paired Student's t-test. N = 5, **P < 0.01, ***P < 0.001 vs. HF group. Notoginsenoside Fe was expressed as Fe.

Fig. 5. I.c.v injection of notoginsenoside Fe affects food intake of obese mice. (A) Food intake of DIO mice after i.c.v injection with saline and notoginsenoside Fe. (B–E) Notoginsenoside Fe induced C-Fos expression in the ARC and PVH of DIO mice, respectively. The data were analyzed by un-paired Student's t-test. N = 5, *P < 0.05, **P < 0.01 vs. saline group. Notoginsenoside Fe was expressed as Fe.