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Obesity as Indirect CVD Risk Factor

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Greater energy deficits-more likely to lose weight; Decreased fasting glucose. ... Repeated attempts at weight loss: 1st VLCD yielded wt. ... – PowerPoint PPT presentation

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Title: Obesity as Indirect CVD Risk Factor


1
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???

2
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

3
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

4
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???

5
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!

6
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.

7
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.

8
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.

9
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.

10
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.

11
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

12
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.

13
Body fat distribution
  • Waisthip ratio-lower fat distributionmales and
    females
  • Upper body fat distribution considered elevated
    males 0.95 females-0.86.

14
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.

15
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.

16
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.

17
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.

18
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

19
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.

20
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.

21
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.

22
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.

23
Women, RT Diet
  • Typical result is to at least maintain if not
    increase FFM with RT.

24
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

25
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

26
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

27
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

28
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.

29
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.

30
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.

31
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.

32
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.

33
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).

34
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.

35
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.

36
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.

37
More training effects
  • Look at training effect of sedentary males
    females. Similar in aerobic capacity BUT females
    had lower fat mass!!

38
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.

39
Protein Diets Weight Loss
  • Potential mechanisms?
  • Potential Side effects?
  • Long-term use?

40
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