Final Flashcards
Where can stem cells be derived from?
Bone marrow, umbilical cord blood, fetal liver, lung. Amniotic fluid, placenta, and adipose tissue
Why is Adispose-derived stem cells better than bone-derived stem cells?
Considerably more effective and convenient alternative to obtain stem cells
Can be collected in very large quantities
Significantly safer and less time consuming
Stem cells have the ability to cross the Blood Brain Barrier
Where can we get adipose derived stem cells?
mesoderm ofAdipocytes, chondrocytes, osteoblast, myocytes, and endothelial cells
Alzheimer’s disease
Associated with accumulation of amyloid 𝜷 plaques and neurofibrillary tangles
Adipose-derived stem cells being injected to the intracerebral region improves memory and reduced amyloid 𝜷 plaque deposition
ALS
Caused by loss of motor neurons in cerebral cortex, brain stem and spinal cord
Symptoms include muscle weakness and atrophy
Death ~5 years after diagnosis and typically due to paralysis of respiratory muscles
Parkinson’s Disease
Common neurodegenerative disorder caused by significant degeneration of dopamine-producing neurons
Results in resting tremor, muscle rigidity, and loss of voluntary muscle control
Where are dopamine cells located?
Substantial nigra
What is the disadvantage of mesenchymal stem cells?
Mesenchymal stem cells proven to promote tumor growth and cancer spread (CCL5 and IGF-1 FoxP2)
Stem Cells can provide drug resistance to cancer therapies (BMP4)
Stem cells have the ability to encourage stem cell properties of cancer cells
CCL
responsible for metastasis of breast and prostate cancer cells
IGF-1
pro-inflammatory peptide that encourages angiogenesis and growth of ovarian tumors
FOXP2
increase potential for metastasis and production of cancer stem cells
BMP4
encourages development of cancer cells and provides it with drug resistance
WHAT IS LIPODYSTROPHY?
Body is unable to produce and maintain healthy fat tissue; abnormal or degenerative conditions of the body’s adipose tissue
What does lipodystrophy cause?
Causes a low amount of Leptin in the blood
What causes lipodystrophy?
– Measles – Pneumonia – Infectious Mononucleosis – Hepatitis – HIV
What is the difference AGL/LAWRENCE SYNDROME AND SIMMONS SYNDROME?
AGL - All fat tissue throughout the body is affected and often can be mistaken for weight loss or gain
SIMMONS-Affects only one area of the body and is not associated with abnormal health generally
results of lipodystrophy?
Low levels of Leptin in the blood can cause fat can accumulate in abnormal locations which include the heart, kidneys, liver and pancreas.
Value of leptin in body
Insulin Resistance Increased Metabolic Rate Protruded Belly High Cholesterol Diabetes Fatty liver disease Pancreatitis Heart Disease Increased appetite
Treatments of lipodstrophy
Leptin Replacement Therapy with human recombinant leptin metreleptin has proven to be an effective therapy to alleviate the metabolic complications.
■ Low fat diet
■ Medical treatment of associated metabolic abnormalities
■ Cosmetic Surgery for appearance
Inflammation
can be endogenous,
it dose not necessarily
involve infection
chronic vs. acute inflammation
Chronic inflammation differ from acute inflammation as it is simultaneous inflammation and repair - a complex interaction between inflammatory cytokines and growth factors that promote healing.
Adipokines
Majority of adipokines are produced by VISCERAL adipose depot (cannot be removed by liposuction
what is the role of marcrophagse
produces cytokines, cluster around
dead and degenerated
adipocytes to engulf
and digest them.
Why is MCP-1 chemokines bad?
promote migration of cells, MCP-1 also activates secretion of TNF-α and IL-6 by macrophages and increases insulin resistance in adipocytes and increase hepatic hyperlipidemia and glucose production, and development of atherosclerotic lesions
IL-6
acute as well as chronic psychological stress tend to increase concentrations of IL-6
TNF-α
TNF-α stimulate the production of IL-6.IL-6, in turn, stimulates the hypothalamo-pituitary–adrenal (HPA) axis.
What does high cortisol cause?
High blood sugar (may lead to diabetes)
High blood pressure
Protein catabolism (the body breaks down it’s own muscle and converts it into sugar for quick energy)
Insomnia (some people who can’t fall asleep)
Anti-inflammatory
Suppresses digestion and the immune system
Hypothyroidism (long term effect of high cortisol)
PAI-1
TNFα (and inflammation in general) increase PAI-1 production by adipose leading to more blood clots b/c PAI-1 inhibits fibrinolysis
Adiponectin
Adiponectin has anti-inflammatory, anti-atherogenic and anti-diabetic properties and HDL levels.
AdipoR1 and 2
1 - in skeletal muscles, bind globular adiopenctin
2 - binds HMW adipoenctin, and in liver
forms of adiponectin
3 main oligomeric forms: LMW, MMW, and HMW
The full-length forms (MMW and HMW) decrease glucose output by the liver
The globular form of adiponectin stimulates β oxidation in muscles
signaling cascade of adiponetin
Adiponectin stimulates
glucose utilization a and fatty acid oxidation by activating AMP-activated protein kinase (AMPK).
What happen to adipocytes when we are overfeeding them?
A Combination of Hypertrophy (decrease adiponectin and Q leading to hypoxia, and increase inflammation) and Hyperplasia
Hypertrophic adipocytes
As larger are the adipocytes, as less oxygen they get, thus hypoxia increases
hypoxia
Hypoxia induces marked changes in the phenotype of macrophages, makes them more inflammatory and increases leptin
visceral fat and heat
Visceral fat is associated with low thermogenesis, and when mice are cold, they eat more
Differences between white and brown fat
brown fat has abundantly more mitochondria and comes from UCP1 which prevents weight gain
What is a free radical?
have one or more unpaired electrons
Where do ROS and RN come from?
mitochondria and produced by obese adipose
Consequences of mitochondrial oxidative stress
decrease membrane fluidity, mutations or deletions of genes, protein aggregation
melanin
Melanin is a strong anti-inflammatory agent (when injected in mice) – it suppresses ILs and TNF-α production
obesity and melanin
Compared with Caucasians and after adjustment for BMI and gender, African Americans had significantly lower odds of severe hepatic pathology
α-MSH
Stimulates the production and release of melanin by melanocytes in skin and hair which absorbs reactive oxygen species and suppresses inflammation .
Central and Peripheral Anorexigenic action as it suppresses appetitis, decrease body weight and food intake
All five melanocortin (MC) receptors for α-MSH are expressed in adipocytes
type sof stress
physiological, environmental, psychological
apotosis
When we have higher cell apoptosis, more oxiDNA is released in the blood this is a hallmark of all chronic and acute pathologies
natural selection
Under the stress, natural selection happen by 1) removing individuals from reproductive pool, including by drops of fertility; 2) selective survival of embryos (others will miscarry)
stress and gender
females received stronger hormonal response to stress, and deal with it by talking. women tend to develop more dangerous types of CVD
ROSE
Mediate stress
microbiome
A multi-genus/species community of bacteria that exists within a defined environmental domain
H.pylori
plays a role in the development of stomach ulcers, but also as a significant risk factor for stomach cancer.
ghrelin
secreted from stomach to indicate hunger, whereas leptin tells us we’re full
metagenomics
first used by Jo Handelsman and it refers to the idea, that a collection of genes sequenced from the environment could be analyzed in way analogous to the study of a single genome
Four places in the human body are the most densely populated with microorganisms
- gastrointestinal tract (800 phylotypes)
- oral cavity (500 phylotypes)
- vagina (200 phylotypes)
- skin (100 phylotypes)
What are the Two most common genera in human guts?
Bacteroidetes and Firmicutes
mice without gut microbial community
produces a rapid and marked increase in adiposity without an increase in food consumption
Western diet was associated with an increased body weight, a lower relative abundance of Bacteroidetes, and a higher relative abundance of Firmicutes.
dysbiosis
microbial imbalance most prominent in the GI tract and skin or even in the vagina, lungs, or head and neck
How antibiotics may cause obesity?
- nutrients are more efficiently absorbed because of a thinner small-intestinal epithelium;
- nutrients are spared because competing microorganisms are reduced;
- microorganisms responsible for subclinical infections are reduced or eliminated;
- production of growth-depressing toxins or metabolites by intestinal microflora is reduced;
- modifications of bacterial enzyme activity improve food efficiency.
Antibody experiment
Firmicutes were shown to be increased in the mice treated with subtherapeutic
doses of antibiotics, and after the experiment they had more body fat then typical
large vs. small intestines
small - absorption of aminoacids, sugars and fats
large - absorption of short-chain FA
cho hypothesis
Antibiotic treatment does not reduce overall bacterial numbers but rather shifts the microbial composition towards species that perform short chain fatty acids (SCFA) fermentation (large intestine), resulting in more efficient energy retrieval from ingested food through more SCFA absorption by the host and increase body mass
What is the Warburg Effect?
This event happens when cells use the glycolysis and fermentation pathway to produce energy instead of the full-on aerobic cellular respiration pathway. Cells that go through this are more than likely cancerous
What happens during the Warburg Effect?
During anaerobic fermentation, cells do not go through the Krebs cycle or oxidative phosphorylation. Instead, it stays in glycolysis (Which the step as a whole does not require the presence of oxygen).
This means that the amount of ATP per glucose molecule drops from 34 down to only 2.
This leads to a decrease in the breakdown of complex molecules and an increase in the synthesis of these molecules.
effects of ketogenic diet on cancer
The goal of using ketogenic diets for cancer treatment is to try and force the body to have oxidative stress on the cancer cells.
In turn, this hopefully will cause the cells to be more sensitive to cancer treatment.
warburg effect
Cells that go through the Warburg Effect don’t go through the Krebs cycle or oxidative phosphorylation. They don’t use oxygen.
cancer cells
Cancer cells go through fermentation and has less ATP.
The result leads to cells not being able to die due to imbalance of ROS.
adenovirus 36
increases adiposity which
increases preadipocyte differentiation and genetic regulation
increases glucose uptake
(E4orf1 protein, and Ras/PI3K/AKT/Glut4 pathway)
Adenovirus 36 also increases the up-regulation of adipogenesis
fat cells with Ad36 vs. without
fat cells with Ad36 DNA had greater adipogenic ability compared to fat cells without AD36 DNA.
E4orf1 protein
This viral protein uses a Ras-mediated pathway to activate PI3K and increases glucose uptake in human primary skeletal muscle cells and in adipose tissue via
bypasses the insulin receptor signaling pathway
improved glucose clearance without increasing sensitivity, production or secretion of insulin (insulin independent)
