Testing the efficacy of - PowerPoint Presentation

Slide1

Testing the efficacy of a green Rooibos extract to counteract the effects of obesogenic feeding on adiposity and rat adipose stem cells.

Principal investigator: Dr H Sadie-Van

Gijsen

1

Collaborators: Dr LM Kotze-

Hörstmann

1

, Dr S

Windvogel

1

, Prof S

Kotze

2

, Dr

P van

Jaarsveld

3

,

Dr R

Johnson

3

,

Prof SS du

Plessis

1

,

Prof B

Huisamen

1

1

Division

of Medical Physiology and

2

Division

of Clinical Anatomy,

Dept

of Biomedical

Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University

3

SA

Medical Research Council,

Parow

ObesityData for South Africa: Overweight (BMI > 25 kg/m2):

70% of women, 40% of men, 25% of children

40% of women obese (BMI > 30 kg/m

2

)

Global Burden of Disease Study 2015: “Attributable deaths and DALYs for high BMI increased substantially, with 645244 more attributable deaths in 2015 than in

2005” (DALY = disability-adjusted life-years: years lived with disability + years of life lost)

DALYs associated with high BMI increased 22% from 2005 – 2015

Co-morbidities: diabetes, hypertension, cardiovascular disease, cancer

We don’t understand: Why can we not just be lean?

We don’t understand

Reason 1: Fat is the enemy! Right??Wrong! Not that simple…..ProtectionEssential storage functionLipodystrophy vs obesity: two sides of the same coin

Produces

circulating factors to regulate metabolism

Subcutaneous

fat:

the good guy (mostly)

Visceral

fat:

the bad guy

Subcutaneous adipose tissue expandability

Bad

news: weight-loss does not always help

Reason 1: Fat is the enemy! Right??Wrong! Not that simple…..Subcutaneous adipose tissue expandability very important, should not be suppressedBad

news:

weight-loss does not always help

We all need a healthy amount of healthy fat tissue to stay healthy

Therefore, the fight against obesity cannot be reduced to a simplistic aim of reducing body weight, fat cell formation or fat content, and “weight-loss” products need to be evaluated for their

effect on fat tissue and fat cell development

and

function

.

Reason 2: inadequate modelsOptions: fat biopsies (only superficial)3T3-L1 cells: one mouse from 1974!SGBS cells: fat overgrowth disorderOther cell lines

All very poor representations!

Cannot mimic whole-body conditions

Primary adipose stem cells (ASCs)Progenitor/precursor cells for new adipocytes (fat cells) within fat tissueProduce circulating factors with metabolic activity

Become dysfunctional during obesity

Can be used to test the effect of

in vivo

interventions (diets, drugs,

etc

) on adipocyte biology

ex vivo

Can compare subcutaneous and visceral fat

Opinion statement: we should all endeavour to use ASCsField survey: who has done what?

Studies published so far using ASCsSeven studies around the world looked at the effects of obesity-inducing diets on ASCs

Studies published so far using ASCsSeven studies around the world looked at the effects of diet-induced obesity on ASCsNO studies done on weight-loss drugs or any botanical products!

Time-line: Male Wistar rats4 weeks after weaning:

Chow

High sugar (HS)

High fat (

HF

)

(n = 24 each)

GRE:

60 mg/kg body weight daily

Lipid analysis

Gene expression

Protein expression

Circulating factors

Chow

Chow-GRE

HS

HS-GRE

HF

HF

-GRE

(n=12 each)

Sample collection:

Body weight

Serum

Blood glucose

Whole hearts

Aortas

Kidneys

Livers, spleens,

pancreataAdipose tissue(subcutaneous, perirenal visceral)(pv weight)Isolation of scASCs and pvASCs

10 weeks

7

weeks

4 weeks

ASC culture

differentiation into fat cells

Main advantages of studyDetailed scientific data on the effects of Rooibos on ASCs during the development of obesity Detailed scientific data on the effects of obesity-inducing diets on ASCs First in SA and Africa

AcknowledgementsAll collaboratorsSA Rooibos Council – main funderNational Research Foundation – co-funderSA Sugar Association – co-funderSU Faculty of Medicine and Health Sciences

(for keeping the lights on!)