Lecture 5: Obesity Flashcards
1
Q
Obesity: Side Notes
A
- Obesity is an exaggeration of normal adiposity and is a central player in the pathophysiology of diabetes mellitus, insulin resistance, dyslipidemia, hypertension, and atherosclerosis, largely due to its secretion of excessive adipokines.
- Obesity is a major contributor to the metabolic dysfunction involving lipid and glucose, but on a broader scale, it influences organ dysfunction involving cardiac, liver, intestinal, pulmonary, endocrine, and reproductive functions.
- Inflammatory, insulin-resistant, hypertensive, and thrombotic-promoting adipokines, which are atherogenic, are counterbalanced by anti-inflammatory and anti-atherogenic adipocyte hormones such as adiponectin, visfatin, and acylation-stimulating protein, whereas certain actions of leptin and resistin are pro-atherogenic.
- Adiponectin is protective against liver fibrosis due to its antiinflammatory effect, whereas inflammatory cytokines such as tumor necrosis factor-α are detrimental for both fatty liver and pancreatic insulin release.
- Obesity contributes to immune dysfunction from the effects of its inflammatory adipokine secretion and is a major risk factor for many cancers, including hepatocellular, esophageal, and colon
2
Q
Functions of The Endocrine System
A
- Differentiation of reproductive system and CNS in fetus
- Stimulation of growth and development
- Coordination of the male and female reproductive systems
- Maintenance of internal environment
- Adaptation to emergency demands of body – fight or flight – high levels of glucose à homeostasis
3
Q
Defining the Obesity Epidemics
A
Difficult to define obesity in a clinical standpoint
Can look at different imaging modalities to look at fat and the location of the adiposity – extracellularly (peripheries) or in intracellularly (in the organs – intramyocellular lipids or fat in the heart)
Imaging (BMI)
- different ways to look at defining obesity
- typically use BMI – a calculation that is body mas per kg relative to their high in meter 2rd
- BMI ranges from low to high in terms of measuring obesity
- Underweight (12-18.5)
- Normal (18.5-25)
- Excessive (30-35)
4
Q
Limitations of BMI
A
- BMI does not look at the fat distribution w/n an individual
- Individuals who have a higher muscle mass may on the BMI scale seem to be overweight or excessively obsess based on the BMI calculation
- BMI may help to define obesity but not help us to look at body composition
5
Q
Mechanisms + Consequences for CVS & Diabetes
A
Atopic fat - can be in and around the heart
6
Q
Risk Factors For Obsesity
A
- Genetics – fairly small 5-10% of cases
- Environmental – family history, types of foods your exposed to, the community you live in, the environment you grow up in, how accessible they are to greenspace and parks so that one could participate in activities, safety
- Physiological – can preexposure us to obesity
- Psychological – poor self esteem, disordered eating à lead to obesity
- Sociological – screen time, habitual physical activity levels, food choices
7
Q
Obesity & Clustering of Risk Factors
A
- Dyslipidemia – high cholesterol
- Hypertension
- Insulin resistance / Impaired glucose tolerance
- Type II diabetes mellitis
- Non-alcoholic steatohepatitis
- Abdominal obesity / Fatty Liver Disease
- Abnormal cholesterol
- Increased BP
- Depression
- Asthma / OSA (obstructive sleep apnea)
8
Q
Inflammatory Adipokines in Obesity
A
- Highlights the role of lipotoxicity and inflammation on obesity
- White adipose tissue à releases a series of adipokines (lipotoxic + inflammatory)
- Adipokines produce inflammation which produces insulin resistance in type 2 diabetes -Associated with infiltration of macrophages and immune dysfunction
- Increase in adipose tissue is associated with particular hormones (i.e. activation + increases we seen in the ROSS system – renin, angiotensinogen, angiotensin tend to be activated and have consequences down the line
- All of the factors combined have a role on obesity and the progression of obesity in other clinical manifestations including diabetes + heart disease + metabolic syndrome
9
Q
A
- Adipose tissues the release of adipokines and macrophages that act to decrease insulin sensitivity
- macrophages also contribute to a enhanced inflammatory sate + as immune stimulators they enhance certain protein kinase and transcription factors –> can play a role in inhibiting the glute for the transporter of glucose = contributing to insulin resistance
- The processive proinflammatory states resulting from obesity + accumulation of adipose tissue promotes the insulin resistance and perpetuates atherogenisis throughout its development – tend to see the dev of plc formation + thrombosis
- The adipokine releases triggers the proliferation of t-cells, NF kappa B à perpetuates inflammation and hyperglycemia
- There are so many implications in the accumulation of adipose tissue and the development of both insulin resistance and atherosclerotic
10
Q
Therapeautic Options: lifestyle modifications
A
- Prescribing and supporting intensive lifestyle modification as the prerequisite for any treatment
- Dietary
- Physical activity
- Behavioral
11
Q
Therapeutic Options: Metformin
A
- AMP kinase activator
- AMP kinase is the metabolic master switch that controls flux through metabolic pathways
- adipocyte lipolysis – breakdown of fat
- skeletal muscle fatty acid oxidation
- stimulation of glucose uptake induced by muscle contraction
- AMPK is also activated by muscle contraction!
- Given to individuals with type 2 diabetes*
- Is similar to exercise*
- Exercise is known to be an ANP kinase activator – promotes the formation of glucose uptake and prevent further weight accumulation*
12
Q
Therapeutic Options: Surgery
A
- Bariatric surgery
- BMI above 50 kg/m2
- BMI above 40 kg/m2 with severe comorbidities
Indicated for adults in cases where lifestyle modifications and therapies have failed
13
Q
Obesity and Implications for CV Disease and Diabetes
A
- Reactive oxygen species + may have an impact on accumulated fat and metabolic syndrome
14
Q
Hypothyroidism
A
- Primary hypothyroidism
- More common
- Due to a disease in the thyroid
- thyroid stimulating levels are high
- Congenital hypothyroidism
- Not as common
- Disease of the hypothalamic and pituitary glands
- Thyroid stimulating levels are low
Is associated with moderate weight gain, is not a major factor in the obesity epidemic
15
Q
Adrenal Cortex
A
- Stimulated by adrenocorticotropic hormone (ACTH)
- Glucocorticoid hormones
- Direct effects on carbohydrate metabolism
- Anti-inflammatory and growth-suppressing effects
- Most potent naturally occurring glucocorticoid is cortisol (associated with stresss)
outer region; is stimulated by the adrenocorticotropic hormone (acts as a precursor for the development of glucocorticoid hormone release
80% of an adrenal gland’s total weight
Zona glomerulosa
Zona fasciculata
Zona reticularis
