Obesity cause/consequence

FIGURE 23-31 Obesity caused by defective leptin production. Both these mice, which are the same age, have defects in the OB gene. The mouse on the right was provided with purified leptin by daily injection, and weighs 35 g. The mouse on the left got no leptin, consequently ate more food and was less active, and weighs 67 g. 

Investigations to understand the metabolic changes caused by obesity are In progress, but it is clear that many of the consequences are due to altered signals arising from the increased mass of adipose tissue. 

Over 5% of the population of western nations is afflicted with diabetes. TTie most prevalent form of diabetes, non-insulin-dependent diabetes mellitus (NIDDM, or type 11), is commonly associated with obesity and hypertension, and is believed to be the consequence of altered insulin action or insulin secretion (for review see Defronzo, 1988 Defronzo and Ferrannini, 1991). Insulin-dependent diabetes mellitus (IDDM, or type 1 diabetes) accounts for approximately 10% of all cases of diabetes. IDDM is characterized by specific destruction of insulin secreting /3-cells found in islets of Langerhans. Destruction of 80-90% of islet /3-cells causes insulin deficiency and the inability to regulate blood glucose levels. 

When cells are continually occupied, they reduce the number of receptors to avoid having the metabolic effects overstimulated. For example, two kinds of diabetes exist, Type I and Type II. Type I diabetes, sometimes called juvenile diabetes, results from the inability of the pancreas to supply insulin. Type II diabetes, sometimes called adult-onset diabetes, is more common and correlates with obesity. In this situation, the body senses itself to be in a well-fed state and releases insulin from the pancreas. The large concentration of insulin causes the recipient cells to be fully stimulated. Consequently, they down-regulate their insulin receptor population to bring the response... 

Pseudotumor cerebri (PTC) is a syndrome characterized by papilledema consequent to increased ICP that is not due to a space-occupying intracranial lesion or other cause. PTC, a diagnosis of exclusion, is seen most frequently in young to middle-aged (10- to 50-year-old) obese women, with a peak incidence in the third decade. 

Finkelstein EA, Ruhm CJ, Kosa KM. Economic causes and consequences of obesity. Annu Rev Public Health 2005 26 239-257. 

Some fundamental differences in obese and lean gut microbiota raise the question of whether the altered gut microbiota is a cause or the consequence of obesity. Although many studies point to a causal role of gut microbiota by demonstrating that GF mice develop obesity if inoculated with obese microbiota while remaining lean if inoculated with lean microbiota, one must keep in mind that the obese microbiota in the donor mice was induced by either HFD or knock-out of certain obesity-related genes. Also, as mentioned above, GF animals mature in terms of their gut physiology, immune-homeostasis and inter-kingdom metabolic pathways in a manner discrete from conventional, microbiota-replete animals. Their response to sudden colonization or their ability to compete for dietary nutrients may, therefore, also be different from that of conventionally reared animals. 

The types of tumour which cause a permanent hypertension, and which may be preceded by a stage of paroxysmal hypertension, frequently simulate essential hypertension or, in the course of a prolonged development, a malignant nephrosclerosis. Alterations in the vascularity of the retina, proteinuria, and an increasing reduction of the renal functions, are the consequences. The relatively frequent occurrence of such symptoms make it necessary to take the phaeochromocytoma into consideration as a possible cause of every hypertension of long duration. It may also be the cause of a diabetes resistance to insulin and accompanied by hypertension, or the simultaneous occurrence of hypertension and an increased basal metabolic rate together with a normal radio-iodine absorption by the thyroid gland. The illness is very improbable in the obese. 

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