Impaired atrial natriuretic peptide-mediated lipolysis in obesity.
BACKGROUND
Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered.


METHODS
Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis.


RESULTS
In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men.


CONCLUSIONS
ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.
Department of Medicine-H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
M
M
Rydén
Department of Medicine-H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
J
J
Bäckdahl
Department of Medicine-H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
P
P
Petrus
Department of Surgery, Karolinska Institutet, Ersta Hospital, Stockholm, Sweden.
A
A
Thorell
Department of of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
H
H
Gao
INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.|University of Toulouse, UMR1048, Paul Sabatier University, France.
M
M
Coue
INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.|University of Toulouse, UMR1048, Paul Sabatier University, France.|Department of Clinical Biochemistry, Toulouse University Hospitals, Toulouse, France.
D
D
Langin
INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.|University of Toulouse, UMR1048, Paul Sabatier University, France.
C
C
Moro
Department of Medicine-H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
P
P
Arner
D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015153:Blotting, Western; D002395:Catecholamines / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008066:Lipolysis; D008297:Male; D017551:Microdialysis; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*
D002395:Catecholamines; D009320:Atrial Natriuretic Factor