2Molecules that Influence Obesity The cause of obesity can be summarized by first law of thermodynamics:“Obesity results when energy intake exceeds energy expenditure”It involves a complex interaction of biochemical, neurologic, environmental, and psychologic factors
3Hormonal controlAppetite is influenced by afferent, or incoming, signals—neural signals, circulating hormones, and metabolites—that impinge on the hypothalamusThese diverse signals prompt release of hypothalamic peptides, and activate outgoing, or efferent, neural signalsAdipocyte also functions as an endocrine cell that releases numerous regulatory molecules, such as leptin, adiponectin, and resistinAdiponectin and resistin, may mediate insulin resistance observed in obesity.
4LeptinStudies of the molecular genetics of mouse obesity have led to the isolation of at least six genes associated with obesityThe most well-known mouse gene, ob, leads to severe hereditary obesity in miceGene's protein product is required to keep the animals' weight under control. The product of the ob gene is a hormone called leptinLeptin is produced proportionally to the adipose mass and, thus, informs the brain of the fat store levelIt is secreted by fat cells, and acts on the hypothalamus of the brain to regulate the amount of body fat through the control of appetite and energy expenditure. Leptin's secretion is suppressed by depletion of fat stores (starvation) and enhanced by expansion of fat stores (well-fed state). Daily injection of leptin causes overweight mice to lose weight and maintain weight loss. The protein also causes weight loss in mice that are not obese
5Leptin ResistanceIn humans, leptin increases the metabolic rate and decreases appetiteHowever, plasma leptin in obese humans is usually normal for their fat mass, suggesting that resistance to leptin, rather than its deficiency, occurs in human obesityThe receptor for leptin in the hypothalamus has been cloned and is produced by a gene known as dbIn rodents, mutation in the db gene produces leptin resistance. However, the mutations thus far described in rodents do not appear to account for most human obesityTherefore, current research is focused on other possible defects in leptin signal transduction in humans
6Other Hormones Ghrelin- A peptide secreted primarily by the stomach It is the only known appetite-stimulating hormoneLevels peak just before meals and drop afterwardInjection of ghrelin increases short-term food intake in rodents, and may decrease energy expenditure and fat catabolismCholecystokinin - Peptides released from the gut following ingestion of a meal can act as satiety signals to the brainInsulin not only influences metabolism, but also promotes decreased energy intake
7Bad News for Dieters Dieting decreases leptin levels Reducing metabolism, stimulating appetiteGhrelinLevels in dieters are higher after weight lossThe body steps up ghrelin production in response to weight lossThe higher the weight loss, the higher the ghrelin levels
8Metabolic Changes Observed in Obesity The metabolic abnormalities of obesity reflect molecular signals originating from the increased mass of adipocytesThe predominant effects of obesity include dyslipidemias, glucose intolerance, and insulin resistance, expressed primarily in the liver, muscle, and adipose tissue
9Metabolic syndromeAbdominal obesity is associated with a threatening combination of metabolic abnormalities that includes glucose intolerance, insulin resistance, hyperinsulinemia, dyslipidemia (low high-density lipoprotein (HDL) and elevated VLDL), and hypertensionThis clustering of metabolic abnormalities has been referred to as the metabolic syndrome, the insulin resistance syndrome, or syndrome XIndividuals with this syndrome have a significantly increased risk for developing diabetes mellitus and cardiovascular disorderFor example, men with the syndrome are three to four times more likely to die of cardiovascular disease.
10DyslipidemiaInsulin resistance in obese individuals leads to increased production of insulin in an effort by the body to maintain blood glucose levelsInsulin resistance in adipose tissue causes increased activity of hormone-sensitive lipase, resulting in increased levels of circulating fatty acidsThese fatty acids are carried to the liver and converted to triacylglycerol and cholesterolExcess triacylglycerol and cholesterol are released as VLDL, resulting in elevated serum triacylglycerolsConcomitantly, HDL levels are decreased.
11Obesity and HealthObesity is correlated with an increased risk of death and is a risk factor for a number of chronic conditions, includingadult onset diabetesHypercholesterolemiahigh plasma triacylglycerolsHypertensionheart diseasesome cancersGallstonesArthritisGoutThe relationship between obesity and associated morbidities is stronger among individuals younger than 55 yearsAfter age 74, there is no longer an association between increased BMI and mortality.
12Weight Loss Weight loss in obese individuals leads to decreased blood pressureDecreased serum triacylglycerolsLow blood glucose levelsHDL levels increaseMortality decreases (particularly deaths due to cancer)Some obesity experts suggest that moderately overweight and otherwise healthy individuals should not obsess about weight loss, but rather should direct their energies to a healthier lifestyle, particularly including some exercise in their weekly routine.
13AssessmentIs he overweight? Obese?What are his key health issues?
14AssessmentAssess the patient's readiness and willingness to lose weight :Unfortunately those who are most concerned about their weights are not necessarily those who are at the highest health risk.Those who are unable or unwilling to embark on a weight reduction program, but they are willing to take steps to avoid further weight gain or perhaps to work on other risk factors such as cigarette smoking, and they should be encouraged to do so.For those not ready to act, the issue should be deferred and brought up at the next visit
15Assessment Measure BMI Measure waist circumference “Apple shape” body is higher risk for DM, CVD, HTNWaist larger than 40 inches for menWaist larger than 35 inches for women
16Weight ReductionThe goals of weight management in the obese patient areto induce a negative energy balance to reduce body weightto maintain a lower body weight over the longer term.
17Treatment Approach A multi-faceted approach is best Diet Physical activityBehavior change
18Treatment Approach Initial goal: 10% weight loss Significantly decreases risk factorsRate of weight loss1 to 2 pounds per weekReduction of caloric intake per daySlow weight loss is more stableRapid weight loss is almost always followed by weight gain
19Treatment Approach Aim for 4 - 6 months of weight loss effort Most people will lose 20 to 25 poundsAfter 6 months, weight loss is more difficultGhrelin & Leptin are at work!Changes in resting metabolic rateEnergy requirements decrease as weight decreasesDiet adherence waversSet goals for weight maintenance for next 6 months, then reassess.
20Behavioral Strategies Keep a journal of diet & activityVery powerful intervention!Set specific goals: behaviorsEatingActivityRelated behaviorsTrack improvementWeigh & measure on a regular basis
21Physical activityAn increase in physical activity can create an energy deficitAlso, increases cardiorespiratory fitness and reduces the risk of cardiovascular disease, independent of weight lossPersons who combine caloric restriction and exercise with behavioral treatment may expect to lose about 5–10% of preintervention body weight over a period of 4–6 months
22Physical ActivityPhysical activity should be an integral part of weight lossPhysical activity alone is less successful than a combined diet & exercise programIncreased activity alonedoes not decrease weightSustained activity doesprevent weight regainReduces risk for heart disease & diabetes
23Physical Activity Start slowly Many obese people live sedentary lives Avoid injuryEarly changes can be activities of daily livingIncrease intensity & duration graduallyLong-term goal30 to 45 minutes or more of physical activity5 or more days per weekBurn calories per week
24Recommend Physical Activity What does it take to burn1000 calories per week?Gardening5 hoursCycling 22 milesRunning11 milesWalking12 milesDancing 3 hours
25Caloric restrictionDieting is the most commonly practiced approach to weight controlCaloric restriction is ineffective over the long term for many individuals. More than 90% of people who attempt to lose weight regain the lost weight when dietary intervention is suspendedNonetheless, it is important to recognize that, although few individuals will reach their ideal weight with treatment, weight losses of 10% of body weight over a 6-month period often reduce blood pressure and lipid levels, and enhance control of Type 2 diabetesThe health benefits of relatively small weight losses should, therefore, be emphasized to the patientWeight loss on calorie-restricted diets is determined primarily by energy intake and not nutrient composition
26Dietary TherapyWeight reduction with dietary treatment is in order for virtually all patients with a BMI who have comorbidities and for all patients over BMI 30.Strategies of dietary therapy include teaching about calorie content of different foods, food composition (fats, carbohydrates, and proteins), reading nutrition labels, types of foods to buy, and how to prepare foods.
27Low-Calorie Step I Diet 1000 to 1200 kcal/day for women1200 to 1600 kcal/day for menAdjust for current weight & activityToo hungry?increase kcal by /dayNot losing?decrease kcal by /day
28How Much is 1200 Calories? Could you stick to 1200 per day? 1 Big Mac (580)1 SMALL Fries (210)1 SMALL shake (430)
29Low-Calorie Step I Diet NutrientRecommended intakeCalories500 to 1000 kcal/day reduction from usualTotal fat<30% of total caloriesCholesterol<300 mg per dayProtein<15% of total caloriesCarbohydrate>55% of total caloriesSodium Chloride<2.4 g sodium, or <6 g sodium chlorideCalcium1000 to 1500 mg/dayFiber20 to 30 g/day
30Weight Maintenance: How Much Should People Eat? Varies widelySome averages, belowMalesAge 20-492900 calories/dayAge 50-plus2500 calories/dayFemales2300 calories/day1900 calories/day
31Pharmacologic treatment Two weight-loss medications are currently approved by the U.S. Food and Drug Administration for use in adults who have a BMI of 30 or higherSibutramine,1 is an appetite suppressant that inhibits the reuptake of both serotonin and norepinephrineOrlistat,2 is a lipase inhibitor that inhibits gastric and pancreatic lipases, thus decreasing the breakdown of dietary fat into smaller molecules
32Pharmacotherapy for Weight Loss Adjunct to diet & physical activityBMI ≥ 30Or, BMI ≥ 27 with other risk factorsShould not be used for cosmetic weight lossOnly for risk reductionUse only when 6-month trial of diet & physical activity fails to achieve weight loss
33Pharmacotherapy for Weight Loss These drugs are only modestly effective2 to 10 kilogram lossMost occurs in the first 6 monthsIf patient does not lose 2 kilograms in the first 4 weeks, success is unlikelyIf the first 6 months is successful, continue medication as long as…It is effective in maintaining weight, andAdverse effects are not serious
34Surgical TreatmantSurgical procedures designed to reduce food consumption are an option for the severely obese patient who has not responded to other treatmentsSurgery produces greater and more sustained weight loss than dietary or pharmacologic therapy, but has substantial risks for complications.
35Weight Loss Surgery Indications 100 pounds overweight or more Or, BMI > 40Or, BMI > 35 and 2 significant comorbiditiesAge 18 to 60Documented failure at nonsurgical effortsPsychological stability
36Weight Loss Surgery Complications of surgery Mortality<1% mortality in healthy young adults BMI < 502-4% mortality in patients with disease and BMI > 60Operative complications< 10%Late complications are uncommonIncisional herniasGallstonesVitamin B12 & iron deficiencyWeight loss failureNeurologic symptoms in unusual cases