Macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis.
OBJECTIVE
Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low-circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice that specifically express the gene coding for human adiponectin in mouse macrophages using the human scavenger receptor A-I gene enhancer/promoter.


RESULTS
Using this transgenic mouse model, we found that adiponectin expression was associated with reduced whole-animal body and fat-pad weight and an improved lipid accumulation in macrophages when these transgenic mice were fed with a high-fat diet. Moreover, these macrophage Ad-TG mice exhibit enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-a (both in the serum and in the metabolic active macrophage), adipose tissue, and skeletal muscle under the high-fat diet condition. Additional studies demonstrated that these macrophage adiponectin transgenic animals exhibit reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with an LDL receptor-deficient mouse model and were fed a high-fat diet.


CONCLUSIONS
These results suggest that adiponectin expressed in macrophages can physiologically modulate metabolic activities in vivo by improving metabolism in distal tissues. The use of macrophages as carriers for adiponectin, a molecule with antidiabetes, anti-inflammatory, and antiatherogenic properties, provides a novel and unique strategy for studying the mechanisms of adiponectin-mediated alterations in body metabolism in vivo.
Luo
Nanlan
N
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Liu
Jian
J
Chung
B Hong
BH
Yang
Qinglin
Q
Klein
Richard L
RL
Garvey
W Timothy
WT
Fu
Yuchang
Y
D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D002352:Carrier Proteins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007328:Insulin / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D000068103:Serine-Arginine Splicing Factors
D052242:Adiponectin; D002352:Carrier Proteins; D018076:DNA, Complementary; D007328:Insulin; C503566:SCAF1 protein, human; D000068103:Serine-Arginine Splicing Factors; D013006:Growth Hormone; D005947:Glucose