Metabolic acidosis lowers circulating adiponectin through inhibition of adiponectin gene transcription.
BACKGROUND
Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as endocrine function. Adipose tissue communicates with the rest of the body through synthesis and release adipokines, such as leptin, adiponectin and TNF-alpha. Adiponectin enhances insulin sensitivity and possesses anti-atherogenic and anti-inflammatory properties. Circulating adiponectin correlates inversely with cardiovascular events. It is possible that MA negatively regulates adiponectin contributing to poor patient outcome. The present study investigates the effect of MA on adiponectin in vivo and in vitro.


METHODS
Twenty healthy female volunteers underwent a 7-day course of oral ammonium chloride (NH4Cl)-induced acidosis. Serum adiponectin was determined before and after NH4Cl ingestion. Adipocytes were differentiated from their precursors, human mesenchymal stem cells (hMSCs), in culture. Concentrated HCl was added to the media to lower pH. Adiponectin mRNA and protein were determined at 48 and 96 h by real-time RT-PCR and ELISA, respectively.


RESULTS
After a 7-day course of NH4Cl, serum bicarbonate decreased significantly associated with the increase in urine ammonium and titratable acid. Adiponectin decreased significantly from 10,623 to 9723 pg/mL (P<0.005). MA suppressed adiponectin mRNA in hMSC-derived adipocytes at 48 and 96 h (P<0.01). The amount of adiponectin released into the culture media declined corresponding to the mRNA levels (P<0.001). MA did not affect adipocyte triglyceride or protein content.


CONCLUSIONS
MA lowered circulating adiponectin through inhibition of adiponectin gene transcription in adipocytes.
Disthabanchong
Sinee
S
Department of Medicine, Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. sineemd@hotmail.com
Niticharoenpong
Kannika
K
Radinahamed
Piyanuch
P
Stitchantrakul
Wasana
W
Ongphiphadhanakul
Boonsong
B
Hongeng
Suradej
S
D000138:Acidosis / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D014158:Transcription, Genetic
D052242:Adiponectin