Hormonal regulation of the human adipose-tissue renin-angiotensin system: relationship to obesity and hypertension.
OBJECTIVE
Adipose tissue secretes vasoactive substances which may contribute to the development of obesity-related hypertension. The aim of this work was to study the expression of renin-angiotensin system genes in adipose tissue of obese hypertensive subjects and the hormonal regulation of these genes.


METHODS
Differential expression of renin-angiotensin system genes in subcutaneous abdominal adipocytes of 12 lean normotensive, eight obese normotensive, and 10 obese hypertensive women was determined in a cross-sectional study. In vitro hormonal regulation of these genes was studied in primary human adipocytes obtained by breast reduction from healthy women.


METHODS
In the clinical study, 24-h ambulatory blood pressure measurement and anthropometry were used to characterize the volunteers, and adipocytes were obtained by subcutaneous needle biopsy. The in vitro regulation of renin-angiotensin system genes by hydrocortisone, insulin, thyroxin, estradiol and angiotensin II on primary cultured human mammary adipocytes was studied by quantitative reverse transcriptase polymerase chain reaction (RT-PCR).


RESULTS
While expression of the angiotensinogen gene was significantly lower in adipocytes from both obese groups, the renin, angiotensin-converting enzyme and angiotensin II type 1 receptor genes were significantly upregulated in obese hypertensives. Hydrocortisone increased angiotensin II type 1 receptor gene and protein expression in a time- and dose-dependent manner in human adipocytes, but had no significant influence on other renin-angiotensin system genes. Expression of these genes was not significantly affected by any of the other tested hormones.


CONCLUSIONS
Renin-angiotensin system genes are differentially regulated in human obesity and hypertension. The role of the adipose-tissue renin-angiotensin system in the development of obesity-associated hypertension or metabolic disease clearly warrants further study.
Gorzelniak
Kerstin
K
Helios Klinkum Berlin, Franz Volhard Clinic - Charité and Max Delbrück Center for Molecular Medicine, Humboldt University of Berlin, Germany.
Engeli
Stefan
S
Janke
Jürgen
J
Luft
Friedrich C
FC
Sharma
Arya M
AM
D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology*; D000328:Adult; D000368:Aged; D002469:Cell Separation; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013851:Thinness; D015854:Up-Regulation
D006728:Hormones; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D006854:Hydrocortisone