Malnutrition/Biological Basis Of Obesity/Leptin And Obesity

Question 1

Protein-energy malnutrition

Answer 1

. Occurs when the amounts of energy (calories) and protein (nitrogen) ingested are insufficient to meet physiological requirements
. Mainly characterized by lack of energy and proteins
. Accompanied by a variety of micronutrient deficiencies

Question 2

Maramus

Answer 2

. Dec. calories intake
. Takes months-years to develop
. Physical exam: cachectic (fat and muscle fasting)
. TSF and MAC depressed
. Weight foe height normal-depressed
. Albumin, transferrin, and total lymphocyte count all normal
. Skin tests normal to depressed
. Clinical course: still have preserved response to short-term stress
. Morality low

Question 3

Kwashiorkor

Answer 3

. Dec. protein intake and stress
. Takes weeks to months to develop
. Physical exam: may appear well nourished, easily pluckable hair, edema
. TSF and MAC relatively preserved
. Weight for height depressed
. Low albumin, transferrin, total lymphocyte count
. Skin tests (immune function) depressed
. Clinical course: infections, poor wound healing, ulcers
. High mortality

Question 4

Mixed malnutrition

Answer 4

. Dec. calorie intake and protein intakes and stress
. Takes a few weeks to develop 
. Physical exam: variable 
. TSF and MAC are variable
. Weight for height depressed
. Skin tests immune) depressed 
. Clinical course variable 
. Mortality variable

Question 5

Adaptations occurring in starvation

Answer 5

. Dec. energy expenditure: rapidly compensated for by dec. in basal energy expenditure, patients exhibit lethargy dec. lean tissue mas also dec. energy requirement
. Mobilization of energy reserves: fat mobilized resulting in Ketosis
. Protein breakdown and synthesis: individual must sacrifice some lean body mass (mainly from skeletal muscle) in order to adjust to the dec. energy requirement

Question 6

. Endocrine changes that occur during starvation

Answer 6

. Endocrine adaptations involving pituitary gland, thyroid gland, adrenal glands, and gonads occur

Question 7

Hematology and oxygen transport during malnutrition

Answer 7

. Combo of a hypometabolism and dec. lean body results in dec. O2 requirement
. Dec. in Hb commonly observed, reflects adaptable response rather than functional anemia

Question 8

Refeeding syndrome

Answer 8

. Refeeding of malnourished patient
. Must be done gradually in order to avoid refeeding syndrome
. Hypophosphatemia, hypokalemia, hypomagnesemia
. Can be fatal and may cause cardiac arrhythmias, confusion, respiratory failure

Question 9

Obesity

Answer 9

. Excess body fat from interaction of genetic, environmental, and behavioral/societal factors

Question 10

Prevalence and health consequences of obesity

Answer 10

. Inc. morbidity and mortality from a variety of medical conditions

Question 11

Waist measurements for obesity

Answer 11

. Over 35 in. Women

. Over 40 in. Men

Question 12

Genetic basis of obesity

Answer 12

. 0.7 heritability for BMI
. Monogenic forms (mutation in LEP gene leading to congenital leptin deficiency) but are rare
. Multifactorial: complex interactions of genes and environment

Question 13

FTO gene and obesity

Answer 13

. Deficiency: leads to delayed postnatal growth, microcephaly, facial dysmorphism, and cardiac abnormalities
. Developmental role as nutrient sensor (essential AA) linked to promotion of gene translation and cell growth

Question 14

Role of FTO in homeostasis

Answer 14

. Variants assoc. w/ BMI and risk for obesity
. Gene expressed in human issues but highest expression observed in brain
. Gene encodes a nuclear localized nuclei acid demethylase, but specific in vivi. Function unknown (dec. transcriptional and translational efficiency)
. Role in energy homeostasis mediated through dysregulation of ghrelin signaling, leading to elevated hunger and impaired postprandial satiety
. Altered hepatic glucose and lipid metabolism leading to inc. hepatic glucose production and triglycerides production

Question 15

FTO variants

Answer 15

. May alter expression of proximal (RPGRIP 1L) and distal (1RX3) genes on the same chromosome
. Lifestyle may modify risks
. Variation in FTO accounts for only 1% of total heritability of BMI

Question 16

Adipokines

Answer 16

. Bioactive peptides secreted by adipose
. Leptin, adiponectin, resistin, visfatin, TNF-alpha and IL-6
. Control appetite/energy expenditure
. Regulate lipid and glucose metabolism
. Modulation of neuroendocrine function
. Overproduction assoc. w/ obesity induces a chronic state of inflammation in adipose tissue and systemically

Question 17

Leptin

Answer 17

. Synthesis stimulated by deposition of TAGs
. Crosses BBB and binds to receptors located w/in hypothalamus
. Leads to dec. activity of AMPK
. Causes inc. signaling via leptin-induced dec. in hypothalamic AMPK activity
. Leads to inc. signaling via appetite-stimulating (orexigenic) neuropeptide Y/AgRP neurons
. Overall effect is to dec. appetite
. Inc. energy expenditure in hypothalamus mediated by inc. sympathetics
. Critical mediator in body-s response to starvation

Question 18

T/F both anorexigenic and orexigenic neurons in ARC express receptors for insulin

Answer 18

T

.

Question 19

Leptin regulation of glucose/lipid metabolism

Answer 19

. Activation of leptin receptors in skeletal m. Plays important role in regulating glucose and lipid metabolism and promoting insulin sensitivity
. Mediated through leptin’s binding to its receptor in the hypothalamus
. Leptin signaling -> phosphorylation/activation of AMPK -> inhibition of acetyl-CoA carboxylase -> inc. FA oxidation -> dec. accumulation of fat in skeletal m. (Lipotoxicity) -> improved insulin sensitivity (enhanced glucose uptake)

Question 20

Differential effects of leptin on AMPK in hypothalamus and skeletal muscle

Answer 20

. In hypothalamus dec. AMPK

. Skeletal muscle: inc. AMPK

Question 21

Leptin neuroendocrine function

Answer 21

. Dec. in blood levels of leptin that occurs during fasting/starvation is assoc. w/ changes in neuroendocrine function
. Major changes included: dec. thyroid hormone, dec. insulin-like growth factor 1, dec. reproductive hormones

Question 22

Pro-inflammatory adipokines

Answer 22

. Released by adipose tissue (leptin, TNF-alpha, IL-6)
. Much interest is focused on how an imbalance btw such pro-inflammatory and adipokines and anti-inflammatory adipokines (adiponectin)
. Important in development of insulin resistance, type 2 DM, cardiovascular disease

Question 23

Adiponectin

Answer 23

. Major adipokine
. Trimmer, hexamer, HMW multimer
. Plasma levels dec. w/ inc. fat deposition
. Implicated in development of metabolic syndrome
. Independent risk factor for type 2 DM, hypertension, atherosclerosis, and MI

Question 24

Adipocytes cell biology

Answer 24

. Adipocytes differentiates from preadipocytes through mitotic cell division
. Under conditions of positive energy balance, ability of adipose to store excess energy as TAGs is dependent upon inc. in adipocytes volume or total number fo adipocytes
. Inc. in adipocytes volume in 1st yr of life
. Inc. in adipocytes number just become teen years
. In weight loss you can only reduce adipocyte volume and not number of them