In mammals, body weight is normally regulated around a set point by coordinated changes in food intake and energy expenditure.
These changes are integrated under the influence of specific neural pathways and circulating signals. Almost 50 years ago it was first proposed that circulating signals generated in proportion to body fat stores influence appetite and energy expenditure in a coordinated manner to regulate body weight.
Of particular historical value are the classic parabiosis experiments which provided evidence that such circulating signals exist.
CITATION Diabetologia. 2003 Feb;46(2):143-72