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Molecular basis of disease > obesity > Flashcards

obesity Flashcards

1
Q

nutritional diseases

A

They are any nutrient-related disease and condition that causes illness in humans
-It includes deficienxies or excesses in diet, eating disorders and chronic diseases such as cardiovascular, hypertension and diabetes
-it is also developmental abnormalities prevented by diet, hereditary metabolic disorders that respond to diets and interaction of foods with drugs, allergies and potentila hazards in the food supply

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2
Q

extreme examples of malnutrition in SA

A

-Poverty and undernourishment results in deficiency of iron, iodine and vitamin A
-Other hand there is poor diet, high fat, refined carbohydrates and sodium that promotes metabolic syndromes of obesity, high blood pressure and insulin resistance

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3
Q

Obesity

A

abnormal or excessive fat accumulation

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4
Q

BMI of overweight

A

obese= >30kg/m2
overweight: 25-29.9kg/m2

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5
Q

World problem of obesity

A

1 billion obese people
Increased by 27% in adults and 47% in children from 1980-2013

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6
Q

obesity related diseases

A

-type 2 diabetes
-non-alcoholic fatty liver disease
-non-alcoholic steatohepatitis
-cardiovascular disease
-cancer
-Increased susceptibility to infectious diseases and poorer outcomes, eg SARS-cov-2

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7
Q

Obesity imbalance

A

Imbalance between caloric intake and energy expenditure
-Caloric intake in excess is stored as fats in adipose tissue as well as glycogen in organs

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7
Q

Adipose tissue

A

Consists of white adipose tissue (WAT) and a small percentage of Brown adipose tissue (BAT)

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7
Q

WAT function

A

-It is an endocrine gland that produces adipokines (hormones) such as leptin and adiponectin which affect glucose and fat metabolism
-It also secretes cytokines that increase/decrease inflation such as TNFalpha, Il1beta, il10

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8
Q

WAT location

A

WAT is distributed all over the body
-Abdomen
-Greates deposists are in omentum, bowl and perenial areas
-Subcutaneous fat is located in buttocks, thighs and abdomen
-different locations have different metabolic and endocrine characteristics

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9
Q

BAT

A

Brown adipose tissue
-It contains many mitochondria and utilises fat to generate heat through uncoupling of electron transport chain by UCP-1
-Process is called adaptive thermogenesis
-BAT represents 1-2% of total body fat and is NB in thermogenesis in babies and maintaining energy homeostasis

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10
Q

Pro inflammatory cytokine

A

IL1beta

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11
Q

Anti-inflammatory cytokine

A

IL10

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12
Q

WAT sensitivity to hormones

A

WAT in the breasts and buttokcs is highly sensitive to eostrogens while WAT in the upperback and neck is sensitive to glucocorticoids
-Visceral WAT has an adipokine secretion profile related to type 2 diabetes and inflammation

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13
Q

Obesity- associated disease drivers

A

-A key driver is the formation of adipose tissue of systemic and persistent (chronic) low grade inflammation
-It is mediated by macrophages and other immune cells that migrate into fatty tissue and produce pro-inflammatory molecules
-Obesity can cause a phenotypic switch of WAT characterised by appearance of inflammed, dysfunctional adipocytes along with infiltration of immune cells
-Immune cells and inflamed adipocytes secrete both locally and systemically, pro-inflammatory cytokine which disrupt normal funcyion of WAT and remote organs

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14
Q

Type I diabetes

A

Autoimmune disease where b-cells in pancreas are destroyed

15
Q

Normal response to high glucose

A

-increased glucose stimulates beta cells in pancreas to make insulin
-Insulin promotes glucose uptake by muscle and fat tissue and signals the fed state

16
Q

Inflammatory cytokine effects

A

Caused by chronic inflammation related by obesity
1) Has a direct effect on adipocyte metabolism and induces insulin resistance and promotes fatty acid release
2)Induces insulin resistance in muscle cells both directly via inhibiting insulin signaling and indirectly via the increased free fatty acids in the blood. Fatty acids are well established to induce insulin resistance in muscle and liver

17
Q

Result of inflammatory cytokine effects

A

-Increased insulin output by pancreas
-Increased blood glucose levels
-Damage associated with above leads to type 2 diabetes

18
Q

type ii diabetes

A

Not absence of insulin but reduced response to insulin

19
Q

Locations of cancer due to obesity

A

Breast, uterine, ovarian, esophagal, stomach, colon/rectal, liver, gallbladder, pancreatice, renal, thyroid

20
Q

Cancer caused by obesity mechanisms

A

-Complex
-Require tumor promoting effects of chronic inflammation signaling in combination with insulin-induced activation of mitogenic signalling pathways since insulin levels are elevated in response to insulin resistance
-DNA damage could occur via increased fatty acid metabolism since this process generates increased oxidative stress and impaired DNA repair mechanisms

21
Q

summarised cancer development

A

inflammatory and mitogenic signalling in combination with oxidative damage may combine to generate transformed cells

22
Q

Obesity association with heart disease and high blood pressure

A

-It is also associated with atherosclerosis which is build up of fat in artery walls leading to formation of plaque
-Obesity causes increased fatty acids and inflammatory cytokines in the blood stream which worsens this process and ultimately results in thrombosis

23
Q

NAFLD

A

-Non-alcoholic liver disease
-hepatocytes in liver become packed with fat
-This may cause liver inflammation (non-alcoholic steatohepatitis or NASH) which can cause liver injury and cirrhosis or liver cancer

24
Q

Obesity causes NAFLD

A

-Increased insulin and blood glucose levels promote fatty acid synthesis in liver
-Fat is usually transported as very low density lipoproteins (VLDLP) to adipose tissue
_Obesity impairs process and causes liver cell fat accumulation
-Increased fatty acids released by adipocytes are taken up by liver and stored as triglycerides which increases liver fat content
-The fat accumulation triggers hapatocyte damage which results in inflammation and hepatitis and may lead to fibrosis and cancer

Molecular basis of disease (12 decks)

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