Genetic factors in obesity

FIGURE 7.12. Changes in body weight after a )Q0-day overfeeding study. Each point represents two persons [twin brothers]. Twelve pairs of twins were studied. The weight increase for one brother may be read from the Y-axis, while that for the other brother is on the X-axis. (Redrawn by permission from Bouchard and Tremblay, 1997.) 

It should be noted that human generics is exquisitely complex. Any person who is fat may be obese because of scv cral, not just one, genetic changes in the body. In addition, the fact that two brothers are twins docs not guarantee that they wdll be genetically identical. A variety of studies have shown that 40-70% of the features of obesity, in humans, are inherited (e.g., Comuzzie and Allison, 1998). 

Several strains of mice have been discovered that are naturally genetically obese. The genetic defects have been traced to specific genes and to changes in the corresponding polypeptides, These polypeptides occur in various tissues in the body, but one thing they have in common is that they all act in the hypothalamus. 

an appreciation of the genetic factors of mouse obe itj requires some background in the physiology of the hypothalamu . 

The -Study of obesity has been aided by the occurrence of certain strains of mice that are genetically obese. These mice arose spontaneously in various animai colonies over the past few decades. Five separate strains have been maintained and bred. Their names and abbreviations are (1) obese (ob), (2) diabetes (db), (3) fat (fat), (4) agouti yellow (A ), and (5) tubby (tub). 

Step 5. C/EBP is a transcription factor of 42 kDa. It binds to a response element with the structure CCAAT. C/EBP forms dimers with itself to generate C/EBP-C/EBP. Activation by PPAR-y is thought to be a primary event in adipoc de formation, with activation by C/EBP being secondary. Evidence suggests that both of these transcription factors act synergistically with each other. 

Step 6. The changes occurring in adipocyte formation include the synthesis and deposition of collagen fibers at the outside surface of the cell, and the synthesis of GLUT-4 transporters, PEPCK, leptin, the insulin receptor, acetyl-CoA carboxylase, and citrate lyase (Smas and Sul, 1995). Adipocytes make a special protein called perilipin, which binds to the outside of lipid droplets. The existence of this protein might be compared with apolipoproteins, which also coat the outside of lipid droplets. A simple assay used to assess conversion of a pre-adipocyte, such as a fibroblast, to an adipocyte is staining with a red dye that binds to lipid droplets (Forman et ah, 1995). 

Genes include the regions of DNA that code for a particular protein or polypeptide, as well as regioris of DNA used to control the rate of transcription. Please find the binding site for a transcription factor on this region of the leptin gene  

A drug is available which binds to PPAR-y and provokes the synthesis of adipocytes. Do you think that this drug would make diabetes better or worse Hint Ask yourself if you think the drug would result in a decline or increase in plasma glucose levels. (See Spiegel-man and Flier, 1996.) 

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Measurement of Body Fat by Skin fold Measurements Measurement of Body Fat by Densitometry Assessment uf Body Fat by Computed Tomography Signaling Pathways for Regulating Adipocyte Formation Genetic Factors in Obesity... 

This chapter provides an overview of the role of gene-environment interactions in obesity. The evidence supporting the role of genetic factors in obesity will first be reviewed followed by a brief description of the methods used to detect gene-environment interactions in human populations and a review of the evidence for a role of gene-environment interactions in obesity. The implications of gene-environment interactions for the prevention and treatment of obesity will also be discussed. 

Genetic Factors in Human Obesity Genetic Factors in Mouse Obesity Obese Gene and Leptin Summary of the t hysiotogy of Adipose Tissue gulation Diabetes Gene and the Lcpiin Receptor... 

Type 2 Diabetes Mellitus This is the most prevalent form of diabetes and is characterized by both an insulin secretion defect and insulin resistance. Maturity-onset diabetes of the young (MODY), attributable to mutations of the glucose kinase gene (discussed earlier), may also be classified as type 2 diabetes mellitus. Obesity is a contributory factor and may predispose to insulin resistance with eventual development of type 2 diabetes mellitus. The precise mechanism by which obesity leads to insulin resistance in the target tissues is not understood. However, in several animal models (e.g., ob/ob mouse, db/db mouse) mutations have been identified that cause both obesity and diabetes mellitus. Unlike type 1 diabetes mellitus, type 2 is not an autoimmune disease. Studies with monozygotic twins have revealed a 90% concordance rate for type 2 diabetes mellitus, suggesting the involvement of genetic factors in the development of the disease. 

Diabetes mellitus is common in old age (Fig. 4). Genetic factors and obesity contribute to the insulin resistance which underlies the development of NIDDM (pp. 56-57). 

Perusse L, Bouchard C. Role of genetic factors in childhood obesity and in susceptibility to dietary variations. Ann. Med. 1999 31 Suppl 1 19-25. 

Farooqi, IS. and S. O Rahilly, 2007. Genetic factors in human obesity. Obes Rev. 8 Suppl 1,37-40. 

Genetic factors appear to be the primary determinants of obesity in some individuals, whereas environmental factors are more important in others. The specific gene that codes for obesity is unknown there is probably more than one gene. 

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