“The Reduced Obese State: The Challenge of Weight

Maintenance”

2011 Annual CAN Conference November 17, 2011

Robert H. Eckel, M.D.

Professor of Medicine

Professor of Physiology and Biophysics

Charles A. Boettcher II Chair in Atherosclerosis

University of Colorado Anschutz Medical Campus

Duality of Interests – Advisory Boards

• Amylin • Esperion • Genentech • Genfit • GTC Nutrition • Johnson & Johnson • Lilly • Merck • Pfizer • Regulus • sanofi-aventis

– Grants/Research Fellowships • Diadexus • GSK • sanofi-aventis

– Educational Venues • AccelMed

• Cardiometabolic Health Congress

• Vindico

• VoxMed

Prevention of Weight Gain

• It’s all a matter of energy balance!

– In the absence of edematous disorders, if you’re burning less than you’re eating you gain weight

E Out < E In

And it’s much less than the 100 kcal/day estimated by Hill JO et al (Science, 2003)

WT

Obesity Incidence Based on

Energy Balance Calculations

• BMI – 25.0 kg/m2, Ht - 68”, Wt – 164 lb

vs.

• BMI – 30.0 kg/m2, Ht – 68”, Wt – 197 lb

over 20 years is

13 kcal/day excess

Body Weight Regulation

SET OR SETTLING POINT?

Body Weight

Time

years months years

therapeutic space prevention

Schematic Representation of the

Natural History of Obesity

Eckel RH, Kahn S et al: Diabetes Care 34:1424 and JCEM 96:1654, 2011

Once obesity occurs, body fat is

defended!

Why is the Defense of Body Fat So Important?

• Body weight (fat mass) is a predictor of

survival in

– Animals

• Mammals

• Birds

• Insects

– Drosophila larvae

– Unfortunate circumstances in humans

• WWII

– Dutch famine, Leningrad

• IRA starvation

Eckel RH. In: Obesity Mechanisms and Clinical Management. pp. 3-30, 2003

Long-Term Follow-Up of Behavioral Treatment for Obesity

Kramer, F.M. et al, Int J Obes 13:131, 1989

Prevalence of Weight Loss Maintenance in a Biracial Cohort: CARDIA

• n = 1869 overweight/obese subjects

– n = 536 (29%) lost 5% between 1995- 2000

• n = 180 (34%) maintained at least 75% between 2000- 2005

• n = 356 (66%) regained

• Predictors of success – African-American race, T2DM, moderate physical activity,

emotional support, reduced sugar-containing soft drinks

• Overall, 34% x 29% = 9% success in those that may have needed weight reduction

Phelan S et al, Am Jour Prev Med 39:546, 2010

Preservation of Weight Loss by Different Interventions

Svetkey LP t al, JAMA 299:1139, 2008

The Biology of Reduced Obesity

• leptin, ghrelin, GLP-1

– appetite

– preference for energy dense foods

• insulin sensitivity

– adipose tissue TG lipolysis

– pro-inflammatory cytokines

– adipose tissue lipoprotein lipase

– skeletal muscle lipoprotein lipase

– CHO oxidation & fat storage

• physical activity Eckel RH, NEJM, 358:18, 2008

Change in Adipose Tissue LPL in

Response to Insulin and/or Corn Oil

Normal Wt Obese Reduced Obese

-2

0

2

4

6

8

10

AT

LP

L (

nm

ol F

FA

/min

/10

6

ce

lls

) Insulin

Insulin + Corn Oil

Eckel RH and Yost TJ, JCI 80:892, 1987

Fasting SMLPL Activity in Normal

Weight and Obese Women

0

2

4

6

SM

LP

L (

nm

ol F

FA

/min

/g)

Normal Obese Weight

before after

p = 0.0001

Eckel RH et al, Eur JCI, 25:396, 1995

ATLPL and SMLPL Responses (0-6h) to a

High-CHO Diet on Changes in Weight and

Fat over 4 Years

Outcome Crude model P Adjusted for sex

and baseline BMI P

Effects of 0-6 h changes in ATLPL activity/cell

Weight change 0.002 0.014 0.751 0.006 0.009 0.332

Fat mass

change

0.049 0.033 0.093 0.040 0.019 0.013

% Fat change 0.049 0.021 0.026 0.036 0.015 0.006

Effects of 0-6 h changes in SMLPL activity/g

Weight change -0.057 0.029 0.060 -0.013 0.019 0.547

Fat mass

change

-0.135 0.067 0.021 -0.048 0.044 0.077

% Fat change -0.077 0.049 0.041 -0.034 0.034 0.056

fMRI, Reduced-Obese > Thin Overfeedng: Hedonic Foods > Basic Objects

Cornier M-Aet al, PLoS ONE, 2009

How much change in AT mass is needed to be

defended?

Let’s ask this question in walking-well normal weight women.

Subject Characteristics

Group Control

(n=18)

Lipectomy

(n=14)

P-value

Race 15C, 2AA,

1H

12C, 1H,

1Asian

NA

Weight (kg) 69.2 6.2 62.3 6.1 <0.005

BMI (kg/m2) 24.8 1.9 23.9 1.7 0.164

Patient Amount Suctioned (mL)

05 4300

06 3650

08 3820

12 2650

14 4445

16 2100

17 950

21 3680

25 1700

27 2900

34 3425

35 2880

38 2575

41 2025

MEAN

2936 ± 272 mL

Suctioning Totals:

Surgery Group

11 women had

suctioning in hips,

thighs, and lower

abdomen below the

umbilicus

3 women had

suctioning in hips

and thighs only

No Difference in Weight between Baseline and 1-Year

Question 1: Does fat come back?

55

60

65

70

75

Baseline 6 wk 6 mo 1 yr

Time

Weig

ht,

kg

Control (n=18) Liposuction (n=14)

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

Control

Lipectomy

Ch

an

ge f

rom

Baseli

ne (

%)

6 wk 12 mo

Question 2: Where does the fat go?

Total Body % Fat Changes: DXA

Hip Circumference

-4

-3.5

-3

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

Control

Lipectomy C

han

ge

s f

rom

Ba

se

lin

e (

cm

)

6 wk 12 mo

Thigh Circumference Changes

-3

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

Control

Lipectomy

Ch

an

ge

s f

rom

Ba

se

lin

e (

cm

)

6 wk 12 mo

Mid Thigh Skin Fold Changes

-12

-10

-8

-6

-4

-2

0

2

Control

Lipectomy

Ch

an

ge

s f

rom

Ba

se

lin

e (

mm

)

6 wk 12 mo

Leg % Fat Changes

-4

-3

-2

-1

0

1

2

Control

Lipectomy

Ch

an

ge

s f

rom

Ba

se

lin

e (

%)

6 wk 12 mo

Subscapular Skin Fold Changes (mm)

-1.5

-1

-0.5

0

0.5

1

Control

Lipectomy

Ch

an

ge

s f

rom

Ba

se

lin

e (

mm

)

Triceps Skin Fold Changes

-0.5

0

0.5

1

1.5

2

2.5

Control Lipectomy

Ch

an

ge

s f

rom

Ba

se

lin

e (

mm

)

6 wk 12 mo

6 wk 12 mo

Changes in Fat by MRI

MRI - Pelvis Relative Fat Area

Changes

-5

-4

-3

-2

-1

0

1

6 wk

6 mo 12 mo

Ch

an

ges f

rom

Baseli

ne (

%)

Control Lipectomy

MRI - Thigh Relative Fat Area

Changes

-8

-6

-4

-2

0

2

6 wk 6 mo 12 mo

Ch

an

ges f

rom

Baseli

ne (

%)

Control Lipectomy

Changes in Abdominal Fat by MRI

MRI - Abdominal Subcutaneous

Relative Fat Area Changes

-6

-4

-2

0

2

4

6 wk

6 mo 12 mo

Ch

an

ges f

rom

Baseli

ne (

%)

Control Lipectomy

MRI - Abdomen Visceral Relative

Fat Area Changes

-

1

-

0.

5

0

0.

5

1

1.

5 6 wk

6 mo

12 mo

Ch

an

ges f

rom

Baseli

ne (

%)

Control Lipectomy

So even in walking-well normal weight women,

total body fat is defended one year after suction lipectomy - and perhaps in less favorable

locations!

Hernandez TL et al, Obesity 19:1388-95, 2011

Energy Intake = Energy Expenditure

Maintenance of Reduced Obesity

Weight Loss Maintenance in the National Weight Control Registry

• Self-reported group of 629 women and 155 men – lost an average of 30 kg – maintained a required minimum weight loss of 13.6

kg for 5 yr

• Weight loss achieved by – 50% a formal program – 50% on their own – Both groups reported having used both diet and

exercise – 77% reported a triggering event – 42% of the sample reported that maintaining their

weight loss was less difficult than losing weight.

Klem ML et al, AJCN 66:239, 1997

Predictors of Weight Loss Maintenance: NWCR

• Energy Intake – avoid frying

– substitute low-fat for high-fat

• Leisure Time Exercise – # of strenuous activities/wk

– # of sweat episodes/wk

• Restraint Scale – Concern about dieting

– Weight fluctuation

McGuire, M.T. et al, Obesity Res 7:334, 1999

Where’s the physician in this whole world of

prevention of weight regain after successful treatment of obesity?

Why Nutrition and Physical Activity Are Not Addressed by Physicians

1. Drugs and devices are available

2. Don’t think lifestyle changes work

3. Not enough knowledge about counseling

4. Insufficient time

5. Not reimbursed

6. Lack of staff (dietitians, exercise therapists)

Eckel RH, Circulation 2006, 13:2657

1. Being better informed about why patients are unsuccessful in losing weight

2. Understanding why they regain it

3. Learning about individual patients to help them modify their lifestyles

The Physician’s Ability to Influence

Weight Loss Depends on:

Eckel RH, Circulation 2006, 13:2657

The 3-Minute Physician Interview • Nutrition

– Daily servings of fruits and vegetables

– Daily servings of whole grains

– Weekly servings of fish

– Saturated and trans fat intake

– Snack foods, desserts

– Maximum weight?

– Food intake pattern

– Weight loss experience

– Weight loss desired?

The 3-Minute Physician Interview

• Physical Activity – Activity in the job place

• elevator, escalator, steps

– Planned activity • type and frequency

– Parking habits • close or far

– Limitations on physical activity – Would you like to increase your

physical activity?

Summary and Conclusions • Once obesity occurs, weight loss is

difficult to achieve and more difficult to

maintain.

– There is a strong metabolic basis for this.

– However, success can be achieved.

• The physician in addition to other

members of the health care team must

be involved.