期刊
NUTRITION & METABOLISM
卷 3, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1743-7075-3-31
关键词
-
资金
- NCRR NIH HHS [C06 RR018823, C06 RR015455] Funding Source: Medline
- NINDS NIH HHS [R01 NS022576, R01 NS040810, R01 NS037766, R01 NS040144, R37 NS022576, R01 NS034741] Funding Source: Medline
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-beta-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 gamma (PPAR gamma), C/EBP alpha 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 PPAR gamma, C/EBP alpha and ADD1/ SREBP1 transcription factors in vivo though PGC1 alpha 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 PGC1a without inhibiting adipocyte-specific transcription factors in DIO mice.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据