Caloric homeostasis

Caloric Homeostasis A Means of Regulating Body Weight... 

The importance of leptin to obesity is dramatically illustrated in mice. Mice lacking leptin are obese and will lose weight if given leptin. Mice that lack the leptin receptor are insensitive to leptin administration. Preliminary evidence indicates that leptin and its receptor play a role in human obesity, but the results are not as clear-cut as in the mouse. The interplay of genes and their products to control caloric homeostasis will be an exciting area of research for some time to come. 

Explain the role of the signaling molecule leptin in maintaining caloric homeostasis and appetite control. 

The term "caloric homeostasis" was coined by Fredickson and Gordon (1958) to express the joint and complementary roles which free fatty acids and glucose play in the blood in supplying the respiration fuel. The interconversion of carbohydrate and fat has been described by Randle et al. (1963) as the glucose-fatty acid cycle (see Figure 2) Reactions 1 and 2 occurs when there is a surplus of carbohydrate (or of ingested fat). Reaction 3 occurs on fasting. The plasma non-esterified fatty acid... 

Current interest in the study of adipose tissue metabolism has been stimulated by the work of many researchers in various countries. It is not my purpose to give a full account of the historical development of the subject, but a few highlights should be mentioned. Among these (a) the demonstration of the rapid turnover of stored fat " (b) the publication in 1948 of the classic review on the physiology of adipose tissue by Wertheimer and Shapiro (c) the identification of the plasma free fatty acids (FFA) as the form in which the triglycerides stored in the adipose tissue are mobilized and made available as fuel to the body tissues, - and the introduction of the concept of caloric homeostasis . ... 

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

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