METABOLIC SYNDROME; EXAMPLE; OBESITY Flashcards
WHAT’S METABOLIC SYNDROME USED TO BE CALLED?
SYNDROME X
WHO INITIALLY NAMED METABOLIC SYNDROME THE SYNDROME X?
GERALD REAVEN
WHAT EXACTLY IS METABOLIC SYNDROME?
A GROUP OF DYSFUNCTIONS THAT INCREASE THE RISK OF DEVELOPING A DISEASE.
A PERSON HAS TO HAVE AT LEAST 3 OF THE FOLLOWING PARAMETERS FOR THE DIAGNOSIS OF METABOLIC SYNDROME:
- INSULIN RESISTANCE OR DIABETES
- HIGH BP
- HIGH FAT IN BLOOD
- LOW HDL, HIGH LDL
- OBESITY
THE METABOLIC SYNDROME INCREASES A PERSON’S RISK OF:
- T2D
- CVD
- CANCER
- NEURODEGENERATIVE DISEASE
THE PARAMETERS OF THE METABOLIC SYNDROME?
- INSULIN RESISTANCE OR DIABETES
- HIGH BP
- HIGH FAT IN BLOOD (TRIGLYCERIDES)
- LOW HDL, HIGH LDL
- OBESITY
% OF CHILDREN 4-5 Y.O. THAT ARE OVERWEIGHT?
10%
% OF CHILDREN 10-11 Y.O. THAT ARE OVERWEIGHT?
20-25%
RATES OF OBESITY IN IMMIGRANTS IN COUNTRIES LIKE THE US USUALLY INCREASE RAPIDLY WITHIN HOW MANY YRS?
5
‘THRIFTY PHENOTYPE THEORY’?
- AIMS TO EXPLAIN WHY PEOPLE, WHEN PUT IN SITUATION WHERE FOOD IS MORE AVAILABLE AND ACTIVITY CHANGES SUDDENLY ACCUMULATE LOTS OF FAT
- PROPOSED THAT PEOPLE WERE ALWAYS PRONE TO BE FATTER IN ORDER TO BE ABLE TO ACCUMULATE RESERVES OF ENERGY IN TIMES OF PLENTY AND BE ABLE TO USE RESERVES WHEN THE TIMES ARE HARDER (KIND OF EVOLUTIONARY ABILITY)
EXAMPLE OF A GROUP THAT DRASTICALLY INCREASED OBESITY AND T2D RATES UPON ACCULTURATION?
THE PIMA PEOPLE, NATIVE AMERICAN TRIBE (USED TO BE FAR FROM OVERWEIGHT, NOW HAVE ONE OF THE HIGHEST OBESITY AND T2D RATES IN THE COUNTRY)
THE MOST COMMON TRAIT TRANSMITTED TO A CHILD BY ITS PARENTS IS?
HEIGHT
WHAT IS A REGRESSION COEFFICIENT AND HOW IS IT USED IN ESTIMATING HERITABILITY?
THE COEFFICIENT ESTIMATES RELATIONSHIP BETWEEN A PREDICTOR VARIABLE AND THE RESPONSE, RANGE 0-1, THE CLOSER IT IS TO 1 THE MORE TRANSMITTABLE/HERITABLE THE TRAIT IS
REGRESSION COEFFICIENT FOR OBESITY?
0.6-0.7 (HIGH HERITABILITY)
% OF VARIATION IN BODY WEIGHT ASSOCIATED WITH GENETIC FACTORS?
70%
WHEN WAS LEPTIN IDENTIFIED?
1994
LEPTIN HAS TONIC EFFECTS. EXPLAIN?
LEVELS OF LEPTIN DO NOT VARY IN SHORT TERM IN RESPONSE TO FOOD BUT RATHER IS A SIGNAL ON THE LEVEL OF OUR ENERGY STORES
WHERE IS LEPTIN RELEASED FROM?
ADIPOSE TISSUE, SO THE LEVELS DIRECTLY RELATE TO LEVELS OF ADIPOSITY
GENETIC MUTATIONS RELATED TO LEPTIN DEFFICIENCIES? EFFECTS? TREATMENT?
- THERE ARE MUTATIONS IN THE LEPTIN GENE THAT CAN INHIBIT ITS PRODUCTION AND LEAD TO OBESITY BECAUSE FOOD INTAKE IS NOT APPROPRIATELY DECREASED WHEN NEEDED
- THERE CAN ALSO BE MUTATIONS IN LEPTIN RECEPTORS ON AgRP AND POMC NEURONS
- LEPTIN CAN BE INJECTED
APART FROM INSULIN RESISTANCE, WHICH OTHER HORMONE CAN OBESE INDIVIDUALS DEVELOP RESISTANCE TO WHICH WILL LEAD TO INCREASED FOOD INTAKE?
RESISTANCE TO LEPTIN
LEPTIN LEVELS IN THE BRAINS OF OBESE PEOPLE ARE LOWER THAN IN LEAN PEOPLE, POSSIBLE REASONS?
- IMPAIRED LEPTIN TRANSPORT ACROSS THE BLOOD BRAIN BARRIER
- IMPAIRED LEPTIN RECEPTORS
- A ROLE OF INFLAMMATION, STRESS AND INEFFECTIVE AUTOPHAGY
LEPTIN RELATED MUTATIONS ARE MONOGENIC OR POLYGENIC?
MONOGENIC
(GWAS) GENOME WIDE ASSOCIATION STUDY IDENTIFIED HOW MANY LOCI IN THE GENOME ASSOCIATED WITH BMI?
97
WHAT HAPPENS IN BRAINS OF OBESE AND LEPTIN RESISTANT INDIVIDUALS WHEN THEY ARE SHOWN PICTURES OF FOOD COMPARED TO LEAN PEOPLE?
- INCREASED ACTIVITY IN THE FOOD CONTROL AREA OF THE HYPOTHALAMUS
- INCREASED ACTIVITY IN BRAIN REWARD CENTRES
OBESITY RELATED COMORBIDITIES/ LONG TERM COMPLICATIONS?
JOINT ISSUES, SLEEP APNEA, ACID REFLUX, INSULIN RESISTANCE, T2D, FATTY LIVER DISEASE, CVD, INFERTILITY
2 GROUPS/TYPES OF OBESE INDIVIDUALS?
MHO - METABOLICALLY HEALTHY OBESE
MUHO - METABOLICALLY UNHEALTHY OBESE
DIFFERENCE BETWEEN MHO AND MUHO:
- ONLY SLIGHT DIFFERENCES IN ADIPOKINES MAIN DIFFERENCES: - INSULIN SENSITIVITY - INFLAMMATION STATE - PRESENCE OR ABSENCE OF VISCERAL FAT AND FAT THAT IS ACCUMULATED IN ORGANS
ORGAN WHERE THERE IS ESPECIALLY HIGH INAPPROPRIATE ACCUMULATION OF FAT IN OBESITY?
THE LIVER
INFLAMMATION PROCESS IN OBESITY, DESCRIBE:
- EXCESSIVE ADIPOSE TISSUE ACCUMULATES
- HYPERTROPHIC ADIPOCYTES ARE UNDER STRESS AND START ATTRACTING IMMUNE CELLS
- THERE IS AN INFILTRATION (AT LEAST IN MUHO) OF IMMUNE CELLS WITHIN ADIPOSE TISSUE
- T CELLS AND MACROPHAGES
- INFLAMMATORY MOLECULES IMPAIR INSULIN SIGNALLING
- INFLAMMATORY SIGNALS INDUCE APOPTOSIS AND NECROSIS IN THE ADIPOSE TISSUE ITSELF
- REDUCE IN FAT CELLS
- INCREASE OF COLLAGEN IN THE ADIPOSE TISSUE, LEADING TO FIBROSIS; REDUCED ABILITY OF ADIPOSE TISSUE TO EXPAND SO THE FAT STARTS ACCUMULATING ESLEWHERE
% OF CELLS IN ADIPOSE TISSUE IN MORBIDLY MUHO THAT ARE IMMUNE CELLS?
UP TO 60%
2 TYPES OF MACROPHAGES PRESENT IN ADIPOSE TISSUE IN OBESITY + WHICH ONE IS MORE PREVALENT?
M1 AND M2
M1 - BAD TYPE, MUCH MORE PRESENT, INCREASES THE INFLAMMATION FURTHER
ACCUMULATION OF WHAT IN ADIPOSE TISSUE LEADS TO FIBROSIS, INABILITY OF THE TISSUE TO FURTHER EXPAND AND ACCUMULATION OF FAT IN ANATOMICALLY INCORRECT PLACES?
COLLAGEN
MHO OCCURS MORE OFTEN IN WHICH SEX AND WHY?
IN WOMEN, BECAUSE OF THEIR NATURAL BODY SHAPE (MORE PEAR)
WHICH TYPE OF FAT IS MORE PROTECTIVE AGAINST THE EFFECTS OF OBESITY?
SUBCUTANEOUS
WHY IS SUBCUTANEOUS FAT MORE PROTECTIVE AGAINST THE EFFECTS OF OBESITY (THAN THE VISCERAL)?
- CAN EXPAND MORE THAN VISCERAL AND THUS PROTECT OTHER ORGANS
- LESS PRONE TO INFLAMMATION BECAUSE IT’S LESS VASULARISED SO IT’S HARDER TO RECRUIT IMMUNE CELLS
- NOT DRAINED BY THE HEPATIC PORTAL VEIN SO THE LIVER IS MORE PROTECTED
WHICH TYPE OF FAT IS DRAINED BY THE HEPATIC PORTAL VEIN?
VISCERAL
LACK OF SUBCUTANEOUS FAT INCREASES RISK OF WHAT?
CVD
WHY DO SOME DEBATE WHETHER SUBCUTANEOUS AND VISCERAL FAT ARE THE SAME TYPE OF ADIPOSE TISSUE?
BECAUSE THEY COME FROM DIFFERENT PRECURSORS
IN WHICH POPULATION ESPECIALLY ARE THE OBESITY RATES INCREASING?
CHILDREN
