Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis.
OBJECTIVE
Similarities in the hepatic responses to obesity and ethanol exposure suggest that these conditions evoke common pathogenic mechanisms. Thus, it is possible that ethanol exposure is increased in obesity. Given that intestinal bacteria can produce ethanol, the aim of this study was to determine if the intestinal production of ethanol is increased in obesity.


METHODS
Breath was collected from genetically obese, ob/ob male C57BL/6 mice and lean male littermates at different ages (14, 20, and 24 weeks) and times of the day (9 AM, 3 PM, and 9 PM). Obese mice (24 weeks old) were then treated with neomycin (1 mg/mL) for 5 days, and sampling was repeated.


RESULTS
Breath collected in the morning from 24-week-old obese mice had a higher ethanol content than breath from their lean littermates (271 vs. 78 pmol/mL CO(2); P < 0.0001). Subsequent studies in 14- and 20-week-old mice showed that exhaled ethanol increased with age in obese (from 26 to 107 pmol/mL CO(2); P < 0. 002) but not lean (29 and 12 pmol/mL CO(2)) mice and was greater in older obese mice than in older lean mice (P < 0.0006). Obese mice showed a diurnal increase in breath ethanol in the morning that decreased through the afternoon and evening (107 to 33 to 13 pmol/mL CO(2)). Neomycin treatment decreased morning breath ethanol levels by 50% (from 220 to 110 pmol/mL CO(2); P < 0.0003).


CONCLUSIONS
Even in the absence of ethanol ingestion, ethanol can be detected in exhaled breath. In obesity, an age-related increase in breath ethanol content reflects increased production of ethanol by the intestinal microflora. Hence, intestinal production of ethanol may contribute to the genesis of obesity-related fatty liver.
Cope
K
K
Departments of Environmental Health and Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Risby
T
T
Diehl
A M
AM
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001835:Body Weight; D001944:Breath Tests; D002940:Circadian Rhythm; D004064:Digestive System / Q000378:metabolism*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D009355:Neomycin / Q000494:pharmacology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values
D000900:Anti-Bacterial Agents; D000431:Ethanol; D009355:Neomycin