Obesity as Indirect CVD Risk Factor

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Obesity as Indirect CVD Risk Factor

• Millions in US are excessively overweight
• 40-50 yr old, 85 elderly diabetics are either
  hypertensive or obese 80 of obese have high BP
  and/or glucose intolerance.
• Syndrome X or Metabolic Syndrome possessing
  three or more of the following Hi BP (SBP130,
  DBP85 Insulin resist.-110 FBGC, Low HDL (males, 50 females), Hi TRIG (150 mg/dl), and
  waist circ. (102 males, 88 females). Now
  obesity (males 22 or 25, females 35 or 39)
  added to profile (Table 9-1).
• Obesity-caused from excess energy intake, genetic
  disposition, and/or inactivity???

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Chapter 26-Weight Management Obesity

• Incidence of other problems associated with
  Obesity- increased insulin response to glucose,
  loss of insulin sensitivity decreased growth
  hormone, HSL, and increased cholesterol
  synthesis
• Category of Obesity-(Table 4-1) Normal BMI is
  18.5-24.9 Overweight- (25.0-29.9) Class I Obese
  (30.0- 34.9) Class II Obese (35- 39.9), Class III
  Obese (40.0)
• body fat-males 25, females-32 for 20-39 yr
  olds

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Exercise Training benefits

• Greater energy deficits-more likely to lose
  weight
• Decreased fasting glucose. insulin, insulin
  resistance, increased glucose tolerance
• Suppresses appetite
• Improves psychological function
• Minimize LBM weight loss
• maintain BMR

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Why is focus usually on eating less?

• Repeated attempts at weight loss 1st VLCD
  yielded wt. loss - (0.47 kg/day) 2nd attempt
  yielded (0.37 kg/day).
• Rats took 21 days to lose 130 grams when overfed,
  and 45 days to regain it. But after second
  overfeeding needed 46 days to lose same 130 grams
  and only needed 14 days to regain it.
• Might diet composition also impact weight
  loss/gain???

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Carbohydrate or Fat the Key??

• Human data supports high fat and/or sugar intake
  also related to adiposity. Dietary saturated fat
  intake also related to body fat. Not related to
  polyunsaturated fat intake.
• Reducing fat intake from 36 to 23 of diet
  reduced body wt 5.8 kg and 3.7 body fat.
• Type of carbohydrate may be important!

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Natural CHO with Fiber

• Studies demonstrate subjects put on restricted
  diets with daily fiber goals usually use more
  weight than those with lower fiber goals.
  Question remains whether it is fiber, per say, or
  simply an increased intake of natural CHOs
  which facilitates weight loss.
• Preventing large decrease in Energy intake also
  appears to be a key-role of BMR.

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Exercise RMR

• Early work supports idea that RMR is similar
  between obese and lean subjects. RMR more related
  to kilograms fat free mass or lean tissue. Even
  when RMR corrected for Body Surface Area.
• Efficiency of absorption of food intake-seems
  same between groups with urine fecal analysis.
  Even when two groups exercise efficiency of cycle
  exercise very similar.

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Contributions to Energy Expended

• Resting Metabolic Rate- 60-75 of total-likely
  affected by activity of thyroid gland. Very rare
  to see difference between trained and untrained
  subjects, or lean vs obese.
• Thermic Effect of Feeding-energy expended in
  processing food. (10). Appears to be
  responders and nonresponders. Suggests that
  moderate levels of PA might help TEF.

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Components of EE (cont.)

• Thermic effect of Physical Activity- How much you
  move daily-widest fluctuation. Might range from
  15-30 of total EE. Typically the largest
  difference between trained untrained, lean vs
  obese. Diet and/or exercise may only change RMR
  and TEF a small amount, but increasing PA creates
  an instant and guaranteed increased EE.

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RMR in Trained Untrained

• Express RMR relative to Fat Free Weight.
• Small difference- 1.15-1.18 in trained vs 1.05
  kcal/kg FFW/hr for untrained. Seems quite
  insignificant but compare over 1 yrs on weight
  regulation.
• Also, what effect does chronic exercise have on
  the EPOC-excess post exercise oxygen consumption.

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POSSIBLE GENETIC DEFECTS FOR OBESITY

• Focus on lower RMR- possible difference in
  subcutaneous vs deep fat distribution-deep fat
  may be more difficult to mobilize and more
  atherogenic.
• 1) Futile metabolic pathways- Glu-G6P - Glu
  Fru-6-P - F 1,6-DP - F 6-P
• 2) Lower turnover of body proteins
• 3) Na-pumping ATPases
• 4) Brown adipose tissue- intrascap., thorax

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ANDROID VS GYNOID

• WAISTHIP RATIO - ANDROID type leads to greater
  incidence of Syndrome X, insulin resistance,
  hyperinsulemia, hyperlipidemia, hypertension.
• 12 yr followup found higher levels of AMI,
  stroke, premature death. Greatest risk was high
  WH ratio and low BMI. Also found in women.
  Central skinfolds more predictive of heart
  disease than thigh.

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Body fat distribution

• Waisthip ratio-lower fat distributionmales and
  females
• Upper body fat distribution considered elevated
  males 0.95 females-0.86.

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Reason for Abdominal Fat Risk

• Storage of fat in abdomen under regulation of
  hormones, enzymes, and fuel sources
• abdominal fat very active-high turnover from
  LPL-leads to high levels of FFA in portal
  circulation of liver.-Might inhibit liver insulin
  uptake due to Inc. triglycerides. Leads also to
  Inc. VLDL-C. Leads to more insulin release.

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MUSCLE FIBER TYPES

• Android related to Type II fibers-less oxidative.
  Low capillary density leads to Inc. insulin
  resistance. Also, lower oxidative capacity to
  metabolize FFA and Triglycerides.
• Gynoid obesity has much less sensitive fat cells-
  need more Epi. to release same amt. of FFA
  Glycerol.

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Endurance Exercise Weight Loss Recommendations

• Exercise alone usually not as effective as when
  combined with dietary modification in magnitude
  of weight loss.
• 700 kcal/day EE resulted in 7.6 kg loss over 3
  mos. 7.4 kg lost when 700 kcal/day dietary
  reduction used.
• Perhaps active individuals compensate by eating
  more.

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Are there Responders vs Non-responders

• Much more variability in weight loss (6.8 times
  more) between identical twins than within twins.
• Role of Leptin UCP-2 in regulating energy
  intake, weight loss will be presented later.

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Exercise Duration Weight Loss

• 30 min of moderate intensity physical activity on
  most, preferably all days of week is ACSM/CDC
  minimum.
• 280 min/wk over 18 mos maintained 13 kg weight
  loss vs 6.5 kg and 3.5 kg for 150-200 and min/wk, respectively.
• 280 min group had no wt gain from mos 6-18 vs
  sig. wt. regain in
• Maintenance of wt loss long-term successful with
  65 min/day of moderate intensity activity

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Exercise Intensity Wt. Loss

• National Weight Control Registry-suggests that
  long-term maintenance of wt loss may be enhanced
  with at least 26 of exercise being vigorous in
  intensity.

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Intermittent Exercise Wt. Loss

• No evidence that it will enhance wt. loss, but no
  negative effect vs traditional continuous
  exercise.
• Proven to be effective in improving exercise
  adherence for initial adoption of exercise in
  overweight men women.

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Lifestyle Activity Wt. Loss

• 16 and 68 wks out lifestyle activity (not a
  planned, structured workout) yielded same wt loss
  as traditional, structured exercise. Same for CV
  fitness improvements.
• Question remains regarding how much of this
  activity must be at least moderate intensity.

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Resistance Training Wt. Loss

• RT should help to maintain FFM during dietary
  restriction thus helping to maintain REE.
• Five studies question how effective RT is on
  maintaining REE during diet-induced wt. loss.
• Combining Endurance Exercise (3 days/wk) with 3
  days/wk periodized RT combined with Energy Intake
  of 1500 kcal/day vs diet endurance ex. vs diet
  alone had greatest impact on improving body
  composition, did not improve wt. loss, blunt
  decrease in RMR or minimize FFM loss. Fat mass
  loss was 69 in diet alone vs 78 in
  dietendurance group 97 for dietenduranceresi
  stance Tr.
• Change in FFM not related to change in RMR.

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Women, RT Diet

• Typical result is to at least maintain if not
  increase FFM with RT.

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Leptin Obesity

• Discovery of the Ob Gene in genetically altered
  mice found a protein called leptin-which
  influences body weight regulation
• No Leptin present-severe obesity
• Mice/Rats-obese animals given injections of
  leptin decrease appetite, increase metabolic
  rate-nice weight loss. Even lean mice given
  leptin lost 15 body weight

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Possible Role of Leptin

• Suppresses bodys response to starvation
• blocks normal drop in EE with decreased caloric
  intake
• BUT- dieting dec. leptin levels, which inc.
  hunger and dec. EE
• Wt. gain Inc. BMR fat mass-leptin
  increases-tries to self-regulate

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Human Response Leptin

• Obese subjects have hi leptin levels- corr. with
  fat mass-called leptin insensitive.
• Perhaps defect in leptin receptor in brain-need
  more leptin for effect to work
• Potential interplay with neuropeptide
  Y-stimulates appetite, CHO intake, insulin
  cortisol

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Other Observations

• 1) Leptin levels corr with visceral fat mass
  plasma insulin levels
• Fat Mass loss corr with dec. Leptin levels, but
  initial leptin levels not predictive of fat mass
  loss

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Leptin Syndrome "X"

• Adipocyte expresses both leptin "TNF-alpha"
  protein, which has ben linked with CVD risk
  factors.
• Elevated TNF-alpha mRNA expression induces
  insulin resistance, slowing insulin receptor
  Glut-4 transport proteins. Reduction in LPL
  activity, activates liver lipolysis, and
  increases plasminogen activator inhibitor-1
  content in adipocytes. Weight loss fat mass
  loss improves insulin sensitivity, lipid
  metabolism, and lowers leptin TNF-alpha levels
  in blood. Question is whether similar trends are
  seen with exercise training.

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Leptin Syndrome "X"

• Studied overweight (BMI range 25-42),
  postmenopausal women who either were put on 1) a
  low energy diet, 2) low energy dietexercise  or
  3) control.
• Three  months of intervention with 6 month
  folllow-up, measures of leptin, body fat, and
  indicies of syndrome X.

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But...what is the leptin syndrome X
relationship??

• Leptin was two-fold higher prior to study
  compared to normal weight women, diet
  dietexercise lowered leptin equally Leptin
  correlated with SHBG plasminogen-activator-inhib
  itor-1, and fat content. Change in leptin corr.
  with change in fat mass. Baseline leptin could
  not predict overall weight loss. Leptin more
  related to fat mass rather than specific to
  syndrome X.

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Results

• Leptin was two-fold higher prior to study
  compared to normal weight women, diet
  dietexercise lowered leptin equally Leptin
  correlated with SHBG plasminogen-activator-inhib
  itor-1, and fat content. Change in leptin corr.
  with change in fat mass. Baseline leptin could
  not predict overall weight loss. Leptin more
  related to fat mass rather than specific to
  syndrome X.

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Leptin moderate-intensity aerobic exercise

• Sedentary males performed 60 min of cycle ex. at
  50 max HR with BMI 284). Measures of leptin
  production serum leptin concentration were
  similar between resting exercise values,
  suggesting that a single bout of exercise may not
  alter leptin activity in sedentary subjects.

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How about more exercise??

• Subjects who exercised for 2 hours after an
  overnight fast had leptin levels drop by 8.3,
  and correlated with increase in plasma free fatty
  acid concentrations (r 0.737). When rested
  refed, leptin levels returned to baseline FFA
  levels dropped below baseline. Just overnight
  fast with no exercise decreased leptin levels
  12.3Ultramarathoners completing event had
  leptin levels decrease by 32, although FFA
  levels not as related to change in leptin (r
  0.366).

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Effect of a Marathon Leptin levels

• Compare 29 male marathoners age/BMI-matched
  controls. Marathoners had lower fat fat mass
  and leptin levels (2.9 vs 5.1 ug/L). Leptin
  relative to fat mass (0.46 ug/L/kg fat mass) was
  similar. Marathon itself reduced leptin to 2.6
  ug/L. Severe change in energy expenditure may
  regulate serum leptin levels.

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Exercise Training Leptin Levels

• Elderly women (60-72 yr) who either remained
  sedentary (C), began exercise (EX) or began
  exercise on hormone replacement therapy (EXHRT)
  for 11 months. Leptin. fat , insulin measured
  pre-post. Leptin decreased by 23 22 in EX and
  EXHRT groups Fat mass most related to leptin
  level (r 0.81) and change in fat mass most
  related to change in leptin levels (r 0.55)
  Insulin related to leptin levels, but also
  related to amount of fat mass. Ratio of
  leptin/fat mass decreased with after weight loss,
  suggesting that fat cell size may be an important
  determinant of leptin levels in women.

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More training effects

• Another study showed a -decrease in leptin levels
  due to training for males but not for females.
  However, the reduction in fat mass could account
  for the decrease in leptin levels. The effect of
  exercise training may be overshadowed by
  changes in fat mass.

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More training effects

• Look at training effect of sedentary males
  females. Similar in aerobic capacity BUT females
  had lower fat mass!!

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Cellular Changes in ob gene Leptin with
Training

• Rats who are genetically obese, insulin
  resistant, and type II diabetic were trained 10
  weeks and compared with trained lean rats
  sedentary controls. Obese rats had 4 fold
  increase in ob mRNA expression compared to lean..
  With training, lean rats decreased ob mRNA
  expression by 85 but obese rats decreased by
  only 50.Fat mass decreased in both exercise
  trained rats, suggesting that a feedback loop
  between the adipocyte and hypothalamus attempts
  to maintain body weight at a constant level by
  reducing ob gene expression in response to
  increased energy expenditure.

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Protein Diets Weight Loss

• Potential mechanisms?
• Potential Side effects?
• Long-term use?

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