Energy Balance Flashcards
the system that controls energy balance involves
- long and short term signals (signals from gut and adipose tissue) that inform the brain of energy status
- brain centers that integrate information
- response: regulation of hunger intensity and energy expenditure
this systems essential role is….
to prevent starvation
how does this system prevent starvation?
ensuring adequate energy intake to compensate for the energy requirements of basal metabolism, physical activity, growth and reproduction
- is biased towards preventing energy deficiency vs preventing excess energy storage
t/f: weight loss makes you predisposed to weight gain
true
signals informing of energy status - insulin
promotes nutrient uptake and storage in peripheral tissues (adipose, skeletal muscle, liver)
- also in the brain: suppresses appetite/increases energy expenditure (but does not regulate brains glucose uptake)
CCK
cholecystokinin
- regulates digestion and reduces appetite
- enteroendocrine cels in duodenum (induced by HCL, amino acids, fatty acids)
- released in response to food
GLP-1
glucagon like peptide
-promotes insulin secretion, reducing glucagon (reducing appetite)
-enteroendocrine cells in ileum/colon in response to nutrients
peptide YY
increases water/electrolyte absorption in colon, reduces appetite
- enteroendocrine cells in ileum/colon in response to fats
CCK, GLP-1, PYY, and ghrelin from the GI tract
peptide hormones with G-protein coupled receptors; exert short-term effects; affect satiation (feeling of fullness)
ghrelin
- hunger hormone
- increases appetite; also stimulates GH release and other effects (reward cognition)
- enteroendocrine cells primarily in stomach (stimulated by fasting, incr, immediately before a meal; suppressed by eating)
leptin
167 aa hormone secreted by white adipose tissue (circulating leptin levels correlate with fat mass)
- suppresses appetite ( among other things - also affects reproductive function, metabolism, inflammation/immune system, etc)
leptin is a ____ of energy stores:
long term indicator, doesnt change with meals, or acutely affect meal size; decreasing leptin levels indicate a negative energy balance/diminishing fat stores, which leads to compensatory responses to replenish these stores
leptin 1950’s
discovery of obese mouse strain with mutant ob gene (increase food intake, obesity, elevated insulin - model of type 2 diabetes)
leptin 1965:
another genetically obese mouse strain bed, with mutation in db gene (same characterisitcs)
leptin 1994
ob gene mapped (expressed in adipose tissue); leptin ‘discovered’
ob/ob mutant mice
food intake/obesity/insulin levels normalize with blood from wild type
db/db mice
must lack a circulating factor (leptin) that controls these phenotypes
db/db mutant mice
high levels of this circulating factor,but cant respond to it; leptin resistant (no receptor)
leptin receptor
- a cytokine receptor
- ligand binding/receptor homodimeriztion leads to JAK2 recruitment and ultimately the activation of STAT3
1994 leptin discovered…
great hope as an anti-obesity treatment
in most cases obese people already have…
high circulating leptin levels, and do not respond to additional exogenous leptin (appear to be leptin resistant)
genetic leptin deficiency is very
rare
hormones indicating energy status:
receptors in hypothalamus and or vagus nerve
two adjacent groups of neurons in _____ of the hypothalamus act as ______
arcuate nucleus, primary site for integrating these inputs (have receptors for gut/adipose tissue)
these two groups of hypothalamis neurons release….
neuropeptides that signal to other parts of hypothalamus and other brain regions
balance of activity of ____ and ____ determines appetite/energy expenditure
NYP- and POMC-expressing neurons
- balance is influenced by relative degree os stimulation or inhibition each type of neuron, and interplay btwn neuron groups
two adjacent groups of neurons in arcuate nucleus of hypothalamus are
- NPY/AgRP expressing neurons
- POMC/Cart-expressing neurons
NYPY/AgRP expressing neurons
- neuropeptides promote appetite (orexigenic)
- stimulated by ghrelin
- inhibited by PYY, CCK, leptin, GLP-2, insulin
POMC/CART expressing neurons
neuropeptides reduce appetite (anorexigenic)
- stimulated by leptin, insulin, GLP-1
- inhibited by NPY from NPY-releasing neurons
orexigenic neuropeptides
- neuropeptide Y - NPY
- agouti-related peptide - AgRP
anorexigenic neuronpeptides
alpha-melanocyte stimulate hormone (a-MSH) which is a posttranslational derivative of pro-opiomelanocortin - POMC, processed by specific proteases
- cocaine- and amphetamine regulated transcript -CART
a-MSH and AgRP act on a common receptor called
melanocortin-4-receptor - MC4R: a-MSH activates it and AgRP is an antagonist
MC4R and NPY receptors
both GPCR
energy expenditure
the brain modulates various processes that consume energy, such as locomotor activity and thermogenesis
- involves neural outputs (sym and parasym NS) and endocrine regulation
- thyroid hormone = key hormonal regulator of metabolism and energy expend
adipose tissue
contains inflammatory/immune cells
adipocytes secretes …
signaling molecules (including hormones, such as leptin and adiponectin) that inhibit or enhance insulin signaling
hormone secretion depends on the amount of lipids stored in
adipocytes, whether a central vs peripheral adipose depot,, inflammation/cytokines ,etc
adiponectin
secreted by adipocytes (inversely correlated with fat mass); improves insulin sensitivity via its effects on liver and muscle
‘full’/enlarged adipocytes release _____ into circulatoin, where they may collect in ____
fatty acids, other cell types, and these ectopic lipid stores affect function of those tissues (inflammation, reduced insulin sensitivity of the tissues, etc)
metabolic syndrome
a cluster of conditions that increase risk of developing heart disease, stroke and/or type 2 diaebetes
maternal obesity and hyperglycaemia are associated with…
long term effects for the offspring, including increased risk of T2d during offsprings adulthood
insufficient nutrion during pregnancy is also problematic….
for health of offspring
- short term effect: fetal growth and development
- potential long term effects include increased risk of t2d during adulthood
