In rat hepatocyte culture, the S14 gene is necessary for induction of lipog
enesis by carbohydrate metabolism and thyroid hormone. To determine if this
gene plays a role in regulation of lipid storage in humans we compared the
response to fasting of the human S14 gene between obese and nonobese subje
cts. We measured the relative content of human S14 mRNA in abdominal subcut
aneous fat before and after a 48-hour fast. We found that mRNA-S14 is stron
gly downregulated in nonobese subjects in response to the fast, but only mi
nimally downregulated in obese subjects. There is an excellent correlation
between the body mass index, and the fasting induced fall in S14 mRNA. Ther
e was no difference in the postfasting glucose, insulin, and ketone levels
between the 2 groups of subjects. Therefore, the S14 gene is abnormally dow
nregulated during fasting in adipose tissue of obese individuals. Further s
tudy of this gene could provide important information on the mechanism of t
he acquisition or maintenance of obesity in humans.