Metabolic lessons from genetically lean mice.

Different types of lean mice have been produced by genetic manipulation. Leanness can result from deficiency of stored energy or a lack of adipocytes to store the lipid. Mice lacking functional adipocytes are usually insulin resistant and have fatty livers, and elevated circulating triglyceride levels. Insulin resistance may result from the lack of adipocyte hormones (such as leptin) and increased metabolite (such as triglyceride) levels in nonadipose tissue. Mice with depleted adipocyte triglyceride levels typically are insulin sensitive and have normal or low liver and circulating triglycerides. Mechanisms to produce depleted adipocytes include increased energy expenditure by peripheral tissues, peripheral mechanisms to decrease food intake, and altered central regulation of these processes.