• The proinflammatory state that is associated with obesity may itself be carcinogenic, through mechanisms discussed in Chapter 6.
Obesityisadisorderofenergyregulation.Itincreasestheriskforanumberofimportantconditionssuchasinsulinresistance,type2diabetes,hypertension,andhypertriglyceridemia,whichareassociatedwiththedevelopmentofcoronaryarterydisease.
Theregulationofenergybalanceisverycomplex.Ithasthreemaincomponents:(1)afferentsignals,providedmostlybyinsulin,leptin,ghrelin,andpeptideYY;(2)thecentralhypothalamicsystem,whichintegratesafferentsignalsandtriggerstheefferentsignals;and(3)efferentsignals,whichcontrolenergybalance.
Leptinplaysakeyroleinenergybalance.Itsoutputfromadiposetissuesisregulatedbytheabundanceoffatstores.LeptinbindingtoitsreceptorsinthehypothalamusreducesfoodintakebystimulatingPOMC/CARTneuronsandinhibitingNPY/AgRPneurons.
Inadditiontodiabetesandcardiovasculardisease,obesityalsoisassociatedwithincreasedriskforcertaincancers,nonalcoholicfattyliverdisease,andgallstones.
The problems of underand overnutrition, as well as specific nutrient deficiencies, have been discussed; however, the composition of the diet, even in the absence of any of these problems, may make a significant contribution to the causation and progression of a number of diseases. A few examples suffice here.
Currently, one of the most important and controversial issues is the contribution of diet to atherogenesis. The central question is whether dietary modification— specifically, reduction in the consumption of foods high in cholesterol and saturated animal fats (e.g., eggs, butter, beef)—can reduce serum cholesterol levels and prevent or retard the development of atherosclerosis (of most importance, coronary heart disease) in those with no previous episode of cardiovascular disease. This is called “primary prevention”. We know some but not all the answers. The average adult in the United States consumes a large amount of fat and cholesterol daily, with a ratio of saturated fatty acids to polyunsaturated fatty acids of about 3:1. Lowering the level of saturates to the level of the polyunsaturates causes a 10% to 15% reduction in serum cholesterol within a few weeks. Vegetable oils (e.g., corn and safflower oils) and fish oils contain polyunsaturated fatty acids and are good sources of such cholesterol-lowering lipids. Fish oil fatty acids belonging to the omega-3, or n-3, family have more double bonds than do the omega-6, or n-6, fatty acids found in vegetable oils. A corollary of this idea is that supplementation of diet with fish oils might protect against atherosclerosis. One study of Dutch men whose usual daily diet contained 30 g of fish showed a substantially lower frequency of death from coronary heart disease than that among comparable control subjects. However, other studies have shown that omega-3 fatty acid supplements do not reduce the risk of cardiovascular diseases, suggesting that yet unknown components of fish may be required for cardioprotection.
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Other specific effects of diet on disease have been recognized:
Restricting sodium intake reduces hypertension.
Dietary fiber, or roughage, resulting in increased fecal bulk, is thought by some investigators to provide a preventive effect against diverticulosis of the colon.
Caloric restriction has been convincingly demonstrated to increase life span in experimental animals, including monkeys. The basis for this striking observation is not clear (Chapter 2).
Even lowly garlic has been touted to protect against heart disease (and also, alas, against kisses—and the devil), although research has yet to prove this effect unequivocally.