Role of Adiponectin and Brain Derived Neurotrophic Factor in Metabolic Regulation Involved in Adiposity and Body Fat Browning

Abstract

Obesity, characterized by excessive fat mass, has been emerging as a major global epidemic and contributes to the increased risk of morbidity around the world. Thus, the necessity to find effective therapy and specific regulatory mechanisms is increasing for controlling obesity. Lately, many researchers have been interested in the linkage between obesity and adipokines/myokines, particularly adiponectin and brain-derived neurotrophic factor (BDNF). However, the role of adiponectin and BDNF in adiposity has not been clearly defined yet. We examined the association of adiposity with adiponectin and BDNF through human study (observational study) with Korean women and in vitro experiments. In the human study, we found a negative relationship between adiposity and circulating adiponectins but irregular patterns in the relationship between adiposity and circulating BDNFs. In the in vitro study using 3T3-L1 adipocytes, adiponectin treatment strongly promoted adipocyte differentiation and the fat browning process, whereas BDNF treatment attenuated adipocyte differentiation and the fat browning process in differentiated adipocytes. Our results demonstrate that adiponectin and BDNF play an important role in regulating fat mass and the expression of fat-browning markers in different ways, and also suggest that circulating adiponectin may be used as an important monitoring index for obesity status.

Keywords: adipocyte; adiponectin; brain-derived neurotrophic factor; fat browning; obesity.

Figure 1

Differentiation protocol of 3T3-L1 cells. BCS: bovine calf serum, Dexa: dexamethasone, DMEM: Dulbecco’s Modified Eagle’s Medium, FBS: fetal bovine serum, IBMX: 1-methyl-3-isobutyl-xantin.

Figure 2

Circulating levels of adiponectin (A) and mature-brain-derived neurotrophic factors (BDNFs) (B) according to obesity status. Means ± S.E. tested by one-way analysis of variance (ANOVA) (p0) and general linear model by Bonfferoni correction with adjustment for age, smoking, drinking, menopausal status, and total calorie intake (p1). Sharing the same alphabet letter (a or b) indicates no statistical significance among the values.

Figure 3

Adiposity estimated by body mass index and waist circumference according to circulating levels of adiponectin (A) and mature-brain-derived neurotrophic factors (BDNF) (B). Means ± S.E. tested by one-way analysis of variance (ANOVA) (p0), and general linear model by Bonfferoni correction with adjustment for age, smoking, drinking menopausal status, and total calorie intake (p1). Sharing the same alphabet letter (a or b) indicates no statistical significance among the values.

Figure 4

Risk of obesity (BMI ≥25 kg/m²) associated with circulating adiponectin concentrations in Korean women. * p < 0.05 compared with the reference group (Q1). The association was calculated using the OR (95% CIs) of a logistic regression model with adjustment for age, smoking, drinking, menopausal status, and total calorie intake; ¹: BMI ≥25 kg/m², CI: confidence interval, OR: odds ratio, Q: quartile.

Figure 5

The effect of Acrp30 (adiponectin) treatment in undifferentiated and differentiated 3T3-L1 adipocyte cells. (A) Adipocyte differentiation and lipid accumulation by Oil red O staining, (B) protein expression related to adipocyte differentiation, (C) mRNA expression of genes involved in body fat browning. Means ± S.E. tested by independent t-test (nonparametric). * p < 0.05, ** p < 0.01, *** p < 0.001, n.s.: no significance; 20 ng/mL treatment of Arp30; undiff: undifferentiated cells, diff: differentiated cells.

Figure 6

The effect of 7,8-DHF (BDNF mimetic) treatment in undifferentiated and differentiated 3T3-L1 adipocyte cells. (A) adipocyte differentiation and lipid accumulation by Oil red O staining, (B) protein expression related to adipocyte differentiation, (C) mRNA expression of genes involved in body fat-browning. Means ± S.E. tested by independent t-test (nonparametric). * p < 0.05, ** p < 0.01, *** p < 0.001, n.s.: no significance; 5 μg/mL treatment of 7,8-DHF; undiff: undifferentiated cells, diff: differentiated cells.