Breaking Down Body Weight: Insights into Metabolic Health and Disease

Protein Science Lead

Merck & Co. (Retired)

Protein Engineering

Distinguished Fellow, Schering-Plough Research Institute (Retired)

Hung V. Le, PhD

https://www.linkedin.com/in/hung-v-le-976740/

Breaking Down Body Weight: Insights into Metabolic Health and Disease

More than just a number

Lifestyle

Genetics

Environment

Understanding the relationship between body weight and metabolic health is important

Body Habitus & Health Risks

Beyond weight: Body habitus refers to the shape, size, and composition of the human body.

Ectomorph

Long, lean

Low muscle mass

Low body fat

Difficulty gaining weight

Mesomorph

Muscular, athletic

Wide shoulder, narrow hip

Gain muscle mass easily

Endomorph

Curvy & soft

More abdominal fat

Lower muscle mass

Summary

1. Weight and appearance could be misleading
2. Body composition (bone, muscle, fat distribution) is more important
3. Fat distribution affects health risk

Metrics for Healthy Weight�Easily Accessible at Home

Waist-to-Height Ratio

Healthy range

0.40-0.49

Obesity

≥ 0.63 (men)

≥ 0.58 (women)

​

Waist-to-Hip Ratio

Healthy range

≤ 0.95 (men)

≤ 0.80 (women)

Obesity

>1 (men)

>0.85 (women)

BMI (Body Mass Index)

Weight /(Height)² [kg/m²]

Healthy range

18.5 - 24.9

Obesity

≥ 30

Preference

Waist-to-Height and/or Hip-to-Waist Ratio

Better assessment of abdominal fat & health risks

​

W

H

W/H

h

W

W/h

H

(Wt)²

H/(Wt)²

Metrics for Healthy Weight�Direct assessment of body fat percentage

Electronic devices

Bioelectrical impedance analysis (BIA)

​

Skin fold Caliper

X-ray Scan

Underwater weighing

(Gold Standard)

Healthy range: 10-20% (men), 18-28% (women)

Obesity: >25% (men), >32% (women)

Fat tissue, function, distribution and types

White fat (bad fat)

Excess energy storage

Abdominal areas Contributes to metabolic diseases

Brown fat (good fat)

Heat generation

Neck and shoulders

Distributed within

body parts/organs

Highest concentration

Subcutaneous

Surrounding organs

Mitochondria

(cell power plant)

High density

Mitochondria

(cell power plant)

Few

The link between abdominal fat and death: What is the shape of health?

From the Harvard Health Blog, February 18, 2021

By Chika Anekwe, MD, MPH, Contributor; Editorial Advisory Board Member, Harvard Health Publishing

Jayedi A, Soltani S, Zargar M S, Khan T A, Shab-Bidar S.

Central fatness and risk of all cause mortality: systematic review and dose-response meta-analysis of 72 prospective cohort studies 

BMJ 2020; 370 :m3324 doi:10.1136/bmj.m3324

Apple Shape

Higher health liabilities

CV Risks: Higher

Risk of Death: Higher

Pear Shape

Lesser health liabilities

CV Risks: Lower

Risk of Death: Lower

Metabolic Syndrome

Reversible!!!

Glucose and Fat Metabolism

Importance of fiber

• Mostly Indigestible
• Feeling full
• Feeds gut microbiome

Small intestine

Site of GLP-1 secretion

Energy source

• Glucose (primary)
• Fat (secondary)
• Protein (last resort)

High energy

requirement

• Muscle
• Brain
• When active!!!

Excess

Glucose>>Glycogen

Stored in liver

Glucose

Overload>>Fatty Acids

Fatty acids>>Triglycerides

Stored in adipose tissue

Insulin (beta-cells)

>>>Glucose absorption

Glucagon (alpha cells)

>>> release glucose & fat

​

Optimizing Nutrition: Your Energy and Macronutrient Metabolism: A Visual Guide. October 4,2023 by Marty Kendall

Glucagon-Like Peptide-1 (GLP-1)

GLP-1-based drug formulations

Injectable for Type 2 Diabetes (e.g. Ozempic, Trulicity..)

Injectable for Weight Management (Wegovy and Saxenda)

Oral for Type 2 Diabetes (Rybelsus)

High Blood Glucose�Protein Glycations

• Disruption of normal protein structure and function
• Increased oxidative stress
• Immune response: Inflammation
• Impaired tissue elasticity (blood vessels, skin, tendons…)
• Skin aging (wrinkles, loss of elasticity,…)
• Diabetic complications (retinopathy, neuropathy, nephropathy, and cardiomyopathy)
• Chronic disease risks (osteoporosis, rheumatoid arthritis, pancreatic cancer,…)

Severe consequences

Basis of HbA1c

High Blood Cholesterol & Triglycerides

• Hardening
• Occlusion
• Clot
• Rupture

Inflammation

Plaque

Formation

Oxidized LDL & Triglycerides�Root causes of Cardiovascular Diseases

Gut Microbes and Weight Gain�Imbalanced microbial composition

Martin AM, Sun EW , Rogers GB , Keating DJ.

The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release

Frontiers in Physiology (2019) 10, 00428. DOI=10.3389/fphys.2019.00428

Healthy microbial population

Beneficial flora>>harmful flora

​

Bad diet

High Refined sugar

High fat

Processed food

Low fiber

Alcohol

Good diet

Low Refined sugar

Low fat

High fiber

High antioxidants

Cause of many diseases

Can affect brain via nervous system

(Gut-brain axis)

TED TALK

How the food you eat affects your gut

The metabolic syndrome is reversible

• Lifestyle change
• Therapeutic intervention
• Surgical options for morbid obesity

Lifestyle Change�A conscious and programmed approach

• Correct information
• Sincere intent
• Coach/Mentor/Community

• Healthy diet
• Calorie restriction
• Fasting style
• Quit smoking
• Limit alcohol intake

• Physical activity intensity
• Moderate: 150min/wk
• High: 75 min/wk
• Strength training
• Stay active all day

Weight management

• Realistic goals
• Periodic tracking

Medical supervision

Frequent check-ups

Stress management

As needed!

Foods that fight inflammation

Howard E. LeWine, MD

March 26, 2024

Harvard Health Publishing/Staying Healthy

​

Anti-inflammatory foods

An anti-inflammatory diet should include these foods:

Foods that cause inflammation

Try to avoid or limit these foods as much as possible:

Therapeutic intervention�Purview of patients & healthcare providers

Certain threshold requires immediate attention

​

​

Hypertensive urgency or emergency (with organ damage)

Blood pressure 180/120 mm Hg or in excess

Hypercholesterolemia guidelines

Triglycerides 500 mg/dL or greater = must treat

Fasting glucose >126 mg/dL (HbA1c >6.5%)= Diabetes = must treat

Weight reduction drug therapy is certainly an option

Early Detection

Warning Signs

Weight gain

Abdominal waist increase

Stress

Inactivity

Sleep apnea

BP rising

Blood tests

Fasting glucose (CMP) or HbA1c

Cholesterol & Triglycerides (Lipid panel)

Optional blood tests

Uric acid

Biomarkers of systemic inflammation

Note

Blood tests available

Over the Counter

But

Best done

with doctors

Weight Gain

Not a

Prerequisite for

Metabolic Syndrome