Research
AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model
1 Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA
2 Department of Pathology, Medical University of South Carolina, Charleston, SC 29425, USA
3 Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic/Foundation, 200 First Street, SW Rochester, MN 55905, USA
4 Department of Pathology and Laboratory Medicine, Ralph Johnson Veterans Affairs Medical Center, Charleston, SC 29425, USA
Nutrition & Metabolism 2006, 3:31 doi:10.1186/1743-7075-3-31
Published: 10 August 2006Abstract
Background
Obesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. The role of AMP-activated protein kinase in adipocyte differentiation is not completely understood, therefore, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK) on adipocyte differentiation in 3T3L1 cells and in a mouse Diet induced obesity (DIO) model.
Methods
To examine the effect of AICAR on adipocyte differentiation in 3T3L1 cells and in a mouse Diet induced obesity (DIO) model, 3T3L1 cells were differentiatied in the presence or absence of different concentration of AICAR and neutral lipid content and expression of various adipocyte-specific transcription factors were examined. In vivo study, treated and untreated mice with AICAR (0.1–0.5 mg/g body weight) were fed high-fat diet (60% kcal% fat) to induce DIO and several parameters were studied.
Results
AICAR blocked adipogenic conversion in 3T3L1 cells along with significant decrease in the neutral lipid content by downregulating several adipocyte-specific transcription factors including peroxisome proliferators-activated receptor γ (PPARγ), C/EBPα and ADD1/SREBP1, which are critical for adipogenesis in vitro. Moreover, intraperitoneal administration of AICAR (0.5 mg g/body weight) to mice fed with high-fat diet (60% kcal% fat) to induce DIO, significantly blocked the body weight gain and total content of epididymal fat in these mice over a period of 6 weeks. AICAR treatment also restored normal adipokine levels and resulted in significant improvement in glucose tolerance and insulin sensitivity. The reduction in adipose tissue content in AICAR treated DIO mice was due to reduction in lipid accumulation in the pre-existing adipocytes. However, no change was observed in the expression of PPARγ, C/EBPα and ADD1/SREBP1 transcription factors in vivo though PGC1α expression was significantly induced.
Conclusion
This study suggests that AICAR inhibits adipocyte differentiation via downregulation of expression of adipogenic factors in vitro and reduces adipose tissue content in DIO mice by activating expression of PGC1α without inhibiting adipocyte-specific transcription factors in DIO mice.
