Summary
Obese-hyperglycaemic mice and lean mice were injected with dichloroacetate to determine
the significance of gluconeogenesis in maintaining the hyperglycaemia of obese mice
and to investigate the effects of a fall in blood glucose on fatty acid synthesis.
One hour after the second of two, hourly, injections of dichloroacetate the blood
glucose concentrations in fed and starved lean mice were decreased, whereas in obese
mice they were sharply increased. In obese and lean mice, both fed and starved, dichloroacetate
decreased plasma lactate but insulin was unchanged. The quantity of liver glycogen
was decreased in all dichloroacetate treated mice, with the largest falls in fed and
starved obese mice, which had much larger glycogen stores than lean mice. Dichloroacetate
treatment decreased the concentration of plasma non-esterified fatty acids in fed
and starved obese mice and fed lean mice but not in starved lean mice. Fatty acid
synthesis in white (inguinal, subcutaneous) adipose tissue was stimulated by dichloroacetate
in fed obese mice and inhibited in fed lean mice. Fatty acid synthesis in brown adipose
tissue (scapular) was faster than in white adipose tissue and was less affected by
dichloroacetate although the changes were in the same direction as in white adipose
tissue. We attribute the increased hyperglycaemia of obese mice treated with dichloroacetate
to increased glycogenolysis coupled with a failure to secrete additional insulin in
response to the raised blood glucose. This high blood glucose concentration in dichloroacetate
treated obese mice may in turn explain the increased fatty acid synthesis in their
white adipose tissue.
Key-Words:
Dichloroacetic acid
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Obese Mice
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Glycogen
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Hyperglycaemia
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Fatty Acid Synthesis
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Brown Adipose Tissue
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White Adipose Tissue
