Final Flashcards
How can weight from a first pregnancy alter the metabolic status of a second pregnancy?
A mother with normal weight at conception might gain excessive weight during her first pregnancy and fail to lose it, resulting in overweight at her second conception.
What is meant by the double burden of malnutrition?
An individual born into too little or poor quality food is now growing up into a world of excessive, high fat food environment.
How does a high fat maternal diet alter maternal behaviour?
Results in inadequate maternal care in mice (spend less time caring for their offspring independent of a variety of other factors) resulting in obesity in offspring, early onset or puberty in female offspring, and an increased ACTH and corticosterone response to restraint stress.
How does maternal high fat alter the early growth trajectory of the offspring?
The pups had a lower birth weight but grew much faster, displaying catch-up growth. They also showed increased fat mass before puberty in showed signs of increase adiposity.
How does maternal high fat nutrition alter the reproductive functioning of their offspring?
Offspring of these mothers show advanced pubertal onset that is exacerbated with a high fat postnatal diet and in girls. This early puberty is linked to obesity and ovarian reserves in girls are effected, aging earlier, altering menstrual cycle and altering the ability to become pregnant.
What is the relationship between perinatal nutrition and MetS risk in adulthood?
Adults offspring of HF-fed moms are obese, hyperleptinemic, hyperinsulinemic, and hypertensive even when fed normal diet through out their lives.
What is the arcuate nucleus?
It is a hypothalamic nuclei. An arc-shaped collections of neuronal cell bodies, they express receptors for many hormones and neuropeptides known to regulate feeding. The ARC interacts with the peripheral circulation through semipermeable capillaries in the underlying median eminence, thus its in an ideal position to integrate hormonal signals for energy homeostasis. It regulates the signals coming in from the gut with the median eminence regulating hormone release.
What is the paraventricular nucleus?
Hypothalamic nuclei. It is the main site of corticotrophin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). It is richly innervated by neuronal protections from the ARC, allowing communication. It plays a role in the integration of nutritional signals with the thyroid and HPA axes.
How do the ARC and the PVN interact?
Projection pathways from the ARC into the PVN allow for the neural control of food intake. When you are full, adipose tissues release leptin, it causes POMC release in the ARC which causes MC4R to be released from PVN. This causes ACTH to be released from the median eminence causing an increase in cortisol release from the adrenal gland, decreasing food intake. When you are hungry, the leptin released triggers NPY release in the ARC, limiting cortisol release and decreasing satiety.
What hormone is key in hunger regulation?
Leptin. It targets neurons in the ARC to decrease food intake and increase energy expenditure.
How does HF effect leptin?
High fat results in increased leptin release but is altered by leptin resistance. The brain doesn’t sense the high leptin levels so the signal to shut down hunger and stop eating never comes. The brain actually believes you don’t have enough leptin so it tells your body to eat more and causes food to look more appetizing.
What occurred when a leptin deficient mouse was treated with leptin in the neonatal period?
Leptin is critical for hypothalamic neuronal circuit formation and the treatment caused an increase in the innervation of PVH by axons form the ARC in neonates, essentially giving leptin back.
What occurred when a leptin deficient mouse was treated with leptin in the late postnatal period?
Found that this did not reverse the phenotype (disruption of A gRR) and the alphaMSH pathway in adults, indicating the critical window of leptin exposure was earlier in pregnancy.
What is the neonatal leptin surge?
Occurring in rodents only, it is the spike in leptin seen after birth that corresponds with the post-natal hypothalamic circuit formation.
How does post-natal nutrition alter hypothal programming?
A large litter saw less milk available and therefore lower neonatal growth but resulted in rapid post weaning weight gain, increased adiposity, and glucose intolerance. It also say a decreased density of alphaMSH and NPY/ArgR fibres (projecting between 2 neurons) in the hypothalamus.
How is leptin related to the HPA axis?
When leptin is in high levels, it inhibits CRH and AVP release from the hypothalamus and cortisol release from the adrenal gland. Cortisol also increases leptin secretion, so as leptin increases, it inhibits cortisol, reducing cortisol and therefore reducing leptin, keeping homeostasis in place.
How are orexic (appetite) mechanisms developed in utero? What does this mean for the fetus?
The development of hypothalamic feeding circuits occur in utero and postnatally. Because of this, adverse perinatal nutrition and hormonal cues can act directly on the brain to regulate activity and development, resulting in altered hypothalamic development, particularly in ARC.
What stimulates swallowing?
Central NPY injection stimulates swallowing of the amniotic fluid in late gestational fetal sheep
What regulates the dipsogenic mechanisms?
The OVLT. It lacks a BBB, therefore the neutrons can respond to osmotic pressure factors present in systemic circulation. They interact with a variety of nuclei in the hypothalamus that are regulating thirst.
How may an adverse intrauterine environment programme appetite or thirst?
Altered development of the orexic or dipsogenic (thirst) centres during critical periods of development may affect normal set points for regulation of appetite and osmoregulation. This may contribute to the programming of hyperphagia or salt preferences, obesity.
How is inflammation related to the HPA axis?
Peripheral and central inflammatory factors can alter HPA function. MetS and obesity are associated with chronic, low grade inflammation, which circulates in the periphery, causing insulin resistance, glucose intolerance, nutrient excess, and finally more cellular inflammation. GCs are important in mitigating these adverse effects.
How can perinatal nutrition effect MetS risk in adulthood?
Whether high or low perinatal nutrition, it results in altered maternal body weight during pregnancy, and therefore altered levels of maternal hormones (GCs). Low nutrition will lead to a premature leptin surge, a lack of leptin, and an increased exposure to GCs. High nutrition will result in maternal hyperleptinemia, leptin resistance, and an increased exposure to GCs. Both result in an increase in NPY and a decrease in POMC, resulting in potentially permanent alteration in hypothalamic wiring. Changes show in cell number, reduced leptin sensitivity, and altered projection development.
In what order to taste responses appear in sheep?
Acid taste by mid
Salt and sweet by late
What is flavour learning?
We learn about flavour by building on the familiar flavour through repeated exposure and increasing complexity (variety) of flavours to which we are exposed. During pregnancy, maternal dietary flavours are transmitted to and flavour the amniotic fluid. Fetal experience of the flavours leads to heightened preferences for these in early postnatal period. Exposures to flavours in breast milk also influence an infant’s liking and acceptance of that flavour as a food. The flavours of weaning foods and subsequently adult foods also affect our flavour preferences.
What occurs with a child’s flavour preference when the mother consumes a high fat diet?
Perinatal exposure to HF, high sugar diet results in preference for palatable food in the offspring resulting in preference for fat, CHO, and protein. In rodents, that has been linked to permanent changes within the central reward (dopaminergic and opioid) pathways that increase the subsequent drive to over consume palatable foods.
Describe the development of the central reward system in humans.
Development of the DA system begins are early as 6-8 weeks of gestation with the opioid system beginning to develop slightly after.
How are preferences for sugars or high fats programmed?
Poor maternal diet causes an increase in transplacental or breastmilk transport of hormones, specifically leptin, insulin, and endogenous opioids, to the offspring. The increase in levels during a critical window will alter the reward system. The DA and opioid signalling pathways may be permanently altered with an increased preference for a suboptimal diet. This leads to consistent or over-consumption, resulting in obesity.
How can preferential perinatal flavour learning be altered?
Breastfed and formula fed infants can learn to like flavours of different foods depending on what and to the degree they are exposed to something.
What is the predictive adaptive response?
Adaptations in utero are done with the assumption that the infant will be born into the same stressful environment. This often results in a mismatch with sufficient/excessive ex-utero environment and places babies at increased risk for developing metabolic diseases in adulthood.
What is the mismatch hypothesis?
Individuals are more likely to suffer from disease if a mismatch occurs between their in utero environment and their postnatal environment. The degree of the mismatch determines the risk of later disease.
Why do not all children exposed to poor pre- or post-natal environments develop disease?
Genetics has a lot to do with this. they may be additive (or protective) to the influence of the early life environment. There is evidence that polymorphisms within genes act as primary contributors of an individual’s risk of disease.
How are genetics associated with obesity?
There is an association between the A allele in the Fat Mass and Obesity Related Locus (FTO) and MBI in childhood. They often show a low BMI in infancy, an early adiposity rebound, and a greater BMI during childhood. This rebound is known to be associated with a risk of adult fat mass and metabolic disease (T2DM). Interestingly, breastfeeding mitigates the impact of these adverse genetics.
Why is breast milk protective against some genetic issues?
Human milk contains nutrients and bioactive molecules. The milk composition changes from the first milk to the end of lactation, with changes in maternal diet, disease state, preterm birth, genetics, and environment. It contains nutrients that are important for brain and gut development that might be missing in formulas.
How do feeding environments effect a childs developmental trajectory?
Programming factors such as milk composition, introduction of complementary feeds, and feeding practices can shape the infants phenotypes. Those that are breast fed gain weight slower and have a lower adiposity than those that use formula or receive early complementary feeding. The difference in hormonal cues from BM may also influence hypothalamic development and connections between the brain and the gut, which can influence distal sites including adipose tissue. The differences in growth and susceptibility to metabolic diseases in breast vs. formula fed infants could arise from different responses of these infants to these types of feeding, or difference exposures to bioactive compounds in BM.
What is the importance of leptin in breast milk?
The BM [leptin] correlates with maternal and infant plasma [leptin]. The BM derived leptin may cue the infant to eat less, slowing weight gain as the leptin binds to receptors in the gastrointestinal epithelium, resulting in satiety signals.
What is the importance of adiponectin in breast milk?
Works opposing leptin and is protective against obesity. It is important in glucose and fatty acid oxidation, although less is known about its role in BM as a postnatal growth factor. It is highly glycosylated in BM, which may protest it from breakdown in the stomach, increasing bioavailability in the infant.
What is the importance of ghrelin in breast milk?
Important in hunger signals. The BM [ghrelin] correlates with the infant serum [ghrelin]. This is unregulated in the infant during periods of rapid growth and correlates with weight and weight gain in the first month of life. This may promote increased appetite and increased E intake, leasing to increase adipose tissue deposition in early infancy. These levels are higher in formula-fed babies.
Why does feeding behaviour matter?
Hormonal cues from breast milk may programme appetite regulation, therefore differences in feeding behaviours and type may influence hypothalamic circuitry development and connections between the gut and brain which can influence distal sites including adipose tissue. Difference in growth and susceptibility to metabolic diseases may arise from responses to different feeding types or exposure to bioactive compounds in breast milk.
What are HOX genes?
Transcription factors that regulate patterning of embryos into regions along the AP axis. This includes some factors that regulate development as well as the gut. Some are expressed in the mesoderm in overlapping patterns whilst some are expressed in the endoderm.
Aside from HOX genes what else are involved in gut patterning?
Some molecules have opposite functions in different areas of the gut, or functions that can change with time even in the same area.
What does the gut come from?
The endoderm.
How do the 3 germ layers form?
Through gastrulation, the 3 germ layers are formed from the epi and hypoblast. The embryo forms an indentation called the primitive streak along the dorsal surface of the epiblast. A node at the end emits growth factors, direct cells to multiply and migrate, flowing the mesoderm and the endoderm, cells remaining in the middle form the ectoderm.
What is gut rotation?
The twisting and movement of the digestive tube during development. The stomach first begins to form along with the small intestine. The pharynx ascends first followed by the descent of the stomach from around the neck to the higher areas. The elongation of the midgut then continues quicker than the rest of the body and the midbrain herniates into the EEC. This allows for the development of the midgut loop in line with the superior mesenteric artery. The stomach twists counter clockwise along the longitudinal axis with the midgut going opposite, causing twisting. At around 6 weeks, the midgut forms cycal buds and begins rotating. At around 10 weeks, everything descends into the final locations and the midgut returns into the cavity.
What types of stem cells are in the intestines?
Putative stem cells. Residing in the crypts, just above the paneth cells. These give rise to all the cells of the gut.
What are the 4 types of cells that putative stem cells give rise to?
Enterocyte, panted, goblet, enteroendocrine cells
What are the secretory cells of the stomach?
Mucous cells: secrete mucous and bicarbonate
Parietal: cells secrete gastric acid (HCl) intrinsic factor
Chief: secrete various enzymes for food breakdown
Endocrine: secrete serotonin, gastrin, glucagon, somatostatin, and other hormones
What is the function of enterocytes?
Columnar cells with apical microvilli that perform hydrolytic and absorptive functions. They also express receptors and other singling molecules involved in the innate immune response.
What is the function of goblet cells?
Located in the middle of the crypt to the tip of the villas, they secrete mucus to protect the stem cells at the base of the crypts.
What is the function of paneth cells?
Columnar epithelial cells with apical granules that hold an innate immune function and are associated with microbial defence by secreting antimicrobial peptides that combat bacteria.
What is the function of endocrine cells?
They produce gastro-intestinal hormones that influence GI secretion, motility, or postprandial satiety.
What triggers the functional development of the gut?
An increase in GCs before and during parturition triggers this as well as several environmental cues during the neonatal period that signal adaptive changes in gut function to facilitate post-weaning survival.
What are the different aspects of gut functional maturation?
Regulation of amniotic fluid volume Motor activity Digestive and absorptive activity Immunity Nutrition
Describe the act of swallowing during gestation.
As the fetus grows, the volume of amniotic fluid swallows increases, starting at around 11 weeks and peaking at about 34 weeks.
How often does amniotic fluid turn over?
The volume turns over every 24 hour. IT is cleared via swallowing.
What is hydramnios?
An inability to swallow that leads to excess amniotic fluid volume.
What occurs if swallowing is prevented?
The gut development becomes delayed. By preventing the passage of injected fluid in sheep during late gestation, it retards the development of the small intestinal mucosa whilst sparing the non-mucosal elements. Although it has no effect on fetal weight, you see reduced SI volume and a lack of fluid in the stomach. Peristalsis is less motile and there is a decrease in mucosal epithelium growth, with shorter villi and an increased villus density.
What occurs if saline is swallowed as opposed to amniotic fluid?
The constituents of the amniotic fluid are trophic for the fetal gut. Saline was less effective at promoting intestinal development. Amniotic fluid in mice has promoted villus growth, crypt development, and premature differentiation of paneth cells.
How does maternal nutrition effect gut development?
Nutrition is a potent trophic stimulus for GIT growth. It supplies nutrients for growth and oxidative metabolism of mucosal epithelial cells as well as indirectly triggering release of growth factors, gut hormones, and activating neural pathways.
What occurs to the gut with improper maternal diet?
Maternal malnutrition and neonatal starvation cause diseases in gut tissue mass, shortened willing, increased catabolism, and decreased protein synthesis.
What is required for proper motor development of the gut?
Integrated neural input
Muscular contractions
Effective peristalsis
Coordination of these with enteral intake
