Fat – good or bad registrartraining2012

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Fat – good or bad? Dr. Katarina Kos Senior Clinical Lecturer Obesity Lead, RD&E Exeter June 2012

Transcript of Fat – good or bad registrartraining2012

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Fat – good or bad?

Dr. Katarina KosSenior Clinical Lecturer

Obesity Lead, RD&EExeter

June 2012

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• What is the definition of obesity and fatness?

• Fat tissue health• Regulation of appetite and adipose tissue

mass: the brain-gut-fat axis

Overview

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1 2 3 4 5

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• Body Mass Index: Body weight (kg)/ height squared (m2)

Definition of obesity

Category (adults) BMI range (kg/m2)

UNDERWEIGHT <18.5

NORMAL 18.5-24.9

OVERWEIGHT 25-29.9

OBESE >30

MORBIDLY OBESE >40

Obesity is an accumulation of fat mass, which is clinically difficult to measure and standardise

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• Waist circumference (cm)

• Waist-to-hip ratio• Skinfold thickness (biceps, triceps, subscapular)• Fat mass (DXA scan, MRI scan or Bodpod)

Determination of ‘fatness’

Men Women

Low <94 <80

High 94-102 80-88

Very high >102 >88

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upper body distribution : android, male, central, upper-body segment, or "apple"

lower body fat distribution: gynoid, female, lower-body segment , or "pear“ shape

What factors determine fat distribution? ◦ Ethnic background◦ Gender◦ Age

Adipose tissue distribution

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Function of adipose tissue

White versus brown fat

•Storage of triglycerides- surplus energy

•Insulation

•Endocrine:• appetite • immunregulation

•Autocrine/paracrine: • immunregulation• FFA regulation: lipogenesis and lipolysis

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Increased FFAdeposition with Insulin

Action of insulin on adipose tissueAction of insulin on adipose tissue

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WAT cell and its productsTriglyceride droplet

Cell nucleus

Macrophage

Endothelial cell

Fatty acidsGlycerol

ChemokinesIL1,IL6, IL10, IL18PAI-1TNFalphaResistinMCP-1

CollagenSPARCVEGFNGF

AdiponectinLeptinVisfatinVaspinChemerinRBP411betaHSDAnigotensinogenEstrogen

Fibroblast

Synapses /Innervation

Kos K, Curr Opinion Invest Drugs, 2009

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Adipokine-related dysfunctionsSkeletal system

Bone Fat deposition

Joints Osteoarthritis, Rheumatoid arthritis, SLE

Muscle Insulin resistance, Ectopic fat deposition

Brain Cerebrovascular disease, Alzheimer's disease, ? Multiple sclerosis

Blood vessels Endothelial dysfunction, Atherosclerosis, Hypertension

Heart Cardiovascular disease, Fibrosis

Immunsystem Systemic inflammation, Sepsis

Liver Hepatosteatosis, Hepatitis, Cirrhosis

Pancreas beta-cell apoptosis, diabetes

GI-tract Inflammatory bowel disease

Kindney Chronic kidney disease, diabetic nephropathy

Lungs Lung injury, COPD

Others: Sleep apnoea syndromeDyslipidaemiaPolycystic ovary syndromeInfertilityCancer

Adipose tissueKos K, Curr Opinon Invest Drugs 2009

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After a 2 year loan to the United States Michelangelo’s David returned to Italy

His proud sponsors were:

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Lean subcutaneous WATObese subcutaneous WAT

Able to expandInflammation

Smaller cells

Hypoxia

Fibrosis

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Fibrosis

Hypoxia Inflammation

Disturbed microcirculation

?

Ectopic fat deposition

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• Liver

• Muscle

• Perivascular

• Epicardial

• Pancreas

• ‘Omental/visceral’

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Lee, et al AMJP 2009

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Congenital LD

Familial partial LD

Acquired LD HIV-relatedHAART-induced

Age at onset birth puberty <20 years any

BMI normal or ↓ normal to ↑ normal to ↑ normal

Genes CGL1(AGPTAT2),CGLT2 (BSCL2)CAV1

FPLD2(LMNA), FPlD3 (PPARG)Akt 2ZIMPSE24

--- ---

Gluteal fat ↓↓↓ ↓↓ ↓ to ↑ 0-↓

Limb fat ↓↓↓ ↓↓↓ ↓↓ 0-↓↓

Trunk fat ↓↓↓ ↑↑↑ 0-↓↓ ↑↑-↓↓

Hepatosteatosis

present possible In generalized LD

possible

Diabetes Very common Depending on mutation

In generalized LD Common

Acanthosis nigricans

present present possible rare

Other Features

Hirsutism, bone cysts. CGLT2: mental retardation, cardiomyopathy

--- Autoimmune disorders, low C3, membranoproliferative glomerolunephritis

--

Modified from Hegele et al, J Lipid Research, 2007

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Congenital LD

Familial partial LD

Aquired LD HIV-related LD

Fasting insulin

↑↑↑ ↑↑ 0-↑↑ ↑-↑↑↑

Triglyceride ↑↑↑ ↑↑↑ 0-↑↑ ↑-↑↑↑

Free fatty acids

unknown 0-↑ unknown ↑↑-↑↑↑

Leptin ↓↓↓ ↓↓ ↓ 0-↑

Adiponectin ↓↓↓ ↓↓ ↓↓ ↓↓

CRP unknown ↑↑ unknown 0-↑

TNFalpha unknown ↑↑ unknown ↑↑↑

Adapted from Hegele et al, J LipidResearch, 2007

Wong S, et al. Diabetologia 2005

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Collagen and insulin resistance

Khan et al, Mol Cell Biol, 2009

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Adiposopathy Fat disorders:

◦ Fat inflammation◦ Fat hypoxia◦ Fat fibrosis◦ Fat ischemia◦ Fat tissue failure

◦ ? Insulin resistance

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'Good' baby fat keeps adults slim

Adults who retain their 'good' baby fat may be buffered against obesity and type 2

diabetes, scientists believe.

Unlike the regular white fat, which stores energy, good brown fat, actively burns calories for heat,

but has been thought only to exist in childhood.

Researchers at the J oslin Diabetes Center not only found adults still had brown fat, but that slim

adults had more of it than fatter ones.

Women appear to have more 'good' brown fat

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Brite fat cells

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Adipose-brain/gut crosstalk

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Liking food is different from wanting food

What makes you eat?

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fMRI image

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Neuronal insulin pathways E.g. NIRKO mice, have

increased feeding behaviour

Reduced insulin evoked response of insulin resistant subjects

Bruning JC, et al. Science 289:2122–2125, 2000Anthony et al, Diabetes 56: 2986-2992, 2006

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Leptin as treatment of obesity?

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Adipose endocrinology

Feedback mechanisms

LeptinAdiponectin?

Hypothalamus

Tractus solitarius

Kos K, et al JCEM 2007

Sympathetic innervation

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Leptin and blood brain barrier

Banks W, AJP, 2002

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Gut hormones: Ghrelin

Effects of three types of macronutrient ingestion on plasma acyl-ghrelin (A) and

total ghrelin (B) levels expressed as a percentage of their respective baseline

values.

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GLP-1What do you know about GLP-

1 metabolism?

GLP-1 receptor in adipose tissue GLP-1 enhances adipogenesispeople with higher expression have

done better after bariatric surgery ( Vendrell J, Endocrinology 2011)

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DPP-IV and fat tissue

Why are DPP-IV inhibitors weight neutral?

Kos K, Diabetes, Obesity and Metabolism, 2009

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DPP-IV expression in abdominal Sc tissue

DP

P I

V m

RN

A e

xpre

ssio

n in

SU

0

50

100

150

200

250

Sc Lean

Sc Obese

*

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SummaryFat tissue is not to be mistaken

by surplus lipidsAdipose tissue is to compensate

for lipotoxicityDietary surplus of FA is

detrimental to metabolic health

Adipose tissue a victim of overeating

‘Not glamorous but essential’

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"You better cut the pizza in four pieces because I'm not hungry enough to eat six.“

Yogi Berra

When picking up his take away pizza:

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