Decrease in brain POMC mRNA expression and onset of obesity in guinea pigs exposed to 2-chloroethyl ethyl sulfide, a mustard analogue.
The full spectrum of physiological effects resulting from exposure to sulfur mustard and its analogs is currently unknown. In a guinea pig model, initially selected to study the role of an inflammatory cytokine cascade in mustard gas induced lung injury, we observed significant body weight gain in guinea pigs exposed to an intratracheally injected single dose of 2-chloroethyl ethyl sulfide, a mustard analog. The body weight gain was not associated with any apparent change in appetite. To further elucidate a molecular basis for the observed weight gain, we evaluated candidate genes for the obese phenotype by quantitative RT-PCR. We observed a time- and dose-dependent decrease in guinea pig pro-opiomelanocortin (POMC) message following treatment with mustard gas. This reduction in POMC message is consistent with the onset of obesity in the animals. We hypothesize that the POMC melanocortin pathway provides a mechanistic basis for the observed effects of sulfur mustard on body weight.
Das
Salil K
SK
Department of Biochemistry, Meharry Medical College, Nashville, TN 37208, USA. sdas@mmc.edu
Chatterjee
Diptendu
D
Mukherjee
Shyamali
S
Grimes
Angela
A
Shen
Yingnian
Y
Smith
Milton
M
Ghosh
Sujoy
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D015536:Down-Regulation; D006168:Guinea Pigs; D008297:Male; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis
D002619:Chemical Warfare Agents; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; C031278:2-chloroethyl ethyl sulfide; D009151:Mustard Gas