Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mas...Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mass is found world-wide as more cultures acquire a Western lifestyle.In the United States,life expectancy declines by 3 years for those with a body mass index over 30 and by 10 years for those with a body mass index over 40 due,in large part,to the increased prevalence of cardiovascular disease.Over the past decade we have come to appreciate that adipose tissue functions as an endocrine organ,and that obesity contributes to cardiovascular and metabolic disorders through cytokine imbalances that promote the development of a chronic,low grade inflammatory state.Bioactive proteins secreted from fat are generally referred to as adipokines.Under conditions of obesity,adipose tissue expresses higher levels of pro-inflammatory adipokines,such as TNF- and IL- 6,and lower levels of anti-inflammatory cytokines. Adiponectin in the prototypical anti-inflammatory adipokine,and its expression is down-regulated in obese individuals.Low adiponectin levels have shown to be an independent risk factor for developing type 2 diabetes,myocardial infarction and hypertension. Studies with genetically manipulated mice have shown that adiponectin protects against the development of a number of diseases that are prevalent in obese individuals including insulin re- sistance,atherosclerosis,LV hypertrophy,and a peripheral artery disease.However,no adiponectin-based therapies have been successfully launched in the clinic due,in large part,to difficulties associated with the high natural abundance of adiponectin (0.01%of the serum protein) and its complex structure.My laboratory performs genetic screens to identify novel adiponectin-like factors involved in metabolic and cardiovascular regulation.One of these newly discovered factors,referred to as Sfrp5, is a secreted protein that is largely produced by adipocytes.Sfrp5 functions by binding to and inhibiting the actions on non-canonical,pro-inflammatory Wnt proteins.We have shown that Sfrp5 and Wnt5a function as a molecular rheostat to control the inflammatory state of the fat pad microenvironment. It is likely that this system also functions to control inflammatory processes that occur in cardio-vascular diseases.展开更多
文摘Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mass is found world-wide as more cultures acquire a Western lifestyle.In the United States,life expectancy declines by 3 years for those with a body mass index over 30 and by 10 years for those with a body mass index over 40 due,in large part,to the increased prevalence of cardiovascular disease.Over the past decade we have come to appreciate that adipose tissue functions as an endocrine organ,and that obesity contributes to cardiovascular and metabolic disorders through cytokine imbalances that promote the development of a chronic,low grade inflammatory state.Bioactive proteins secreted from fat are generally referred to as adipokines.Under conditions of obesity,adipose tissue expresses higher levels of pro-inflammatory adipokines,such as TNF- and IL- 6,and lower levels of anti-inflammatory cytokines. Adiponectin in the prototypical anti-inflammatory adipokine,and its expression is down-regulated in obese individuals.Low adiponectin levels have shown to be an independent risk factor for developing type 2 diabetes,myocardial infarction and hypertension. Studies with genetically manipulated mice have shown that adiponectin protects against the development of a number of diseases that are prevalent in obese individuals including insulin re- sistance,atherosclerosis,LV hypertrophy,and a peripheral artery disease.However,no adiponectin-based therapies have been successfully launched in the clinic due,in large part,to difficulties associated with the high natural abundance of adiponectin (0.01%of the serum protein) and its complex structure.My laboratory performs genetic screens to identify novel adiponectin-like factors involved in metabolic and cardiovascular regulation.One of these newly discovered factors,referred to as Sfrp5, is a secreted protein that is largely produced by adipocytes.Sfrp5 functions by binding to and inhibiting the actions on non-canonical,pro-inflammatory Wnt proteins.We have shown that Sfrp5 and Wnt5a function as a molecular rheostat to control the inflammatory state of the fat pad microenvironment. It is likely that this system also functions to control inflammatory processes that occur in cardio-vascular diseases.
