Adipose Tissue Flashcards
Locations of adipose
. SubQ
. Visceral
. Bone marrow
. Structural
Brown adipose tissue
. Contains cells w/ multiple lipid droplets interspersed among abundant mitochondria
. Completes non-shivering thermogenesis
. In adults it is located in upper chest and neck
. Becomes more active w/ cold exposure via adrenergic stimulation
. Plays functional role in temperature control
White adipose tissue
. Contain 1 very large droplet of white fat in cytoplasm
. Main function is long-term energy storage
. Fibroblasts, macrophages, and other cells make up about half the total number of cells
Regulation of adipogenesis
. Retains ability to grow in adulthood
. Inc. in size occurs through precursor proliferation, maturation, lipid storage/release from adult adipocytes and apoptosis
. Adipocyte precursors derived from pericytes located just outside the capillaries, transform into preadipocytes or stromatolites cells that can differentiate into white or brown adipocytes
Activators of adipogenesis
. GH . IGF-1 . insulin . Cortisol . Thyroid hormone . Retinoic acids . Endogenous peroxisome proliferator-activated receptor-gamma ligand (PPAR-gamma) . Prostaglandin PGJ2
Inhibitors of adipogenesis
. Tumor necrosis factor . Interferon y . Preadipocyte factor pref-1 . Resistin . Transforming growth factor beta
PPAR-gamma
. Inc. expression of genes for glucose uptake, lipid uptake, and lipid synthesis pathways
How triglycerides are stored in adipocyte
. Cytoplasmic droplets coated by layer of phospholipids and proteins
. Coat sequesters the lipids from cytosol and regulate the access of lipases to the surface of the droplet
. One coated proteins (perilipin) can be phosphorylated by PKA and PKG initiating the process of lipolysis
Glucocorticoid signals to adipose tissue
. High levels ACTH and glucocorticoids result in obesity
. Enzyme 11HSD-1 present in human adipose tissue and converts inactive cortisone into active cortisol
. Strong positive correlation btw adipocytes size and activity of 11 HDS-1 in converting cortisone into cortisol
Growth hormone/insulin-like growth factor-1 (IGF-1)
. Potent lipolysis hormone through activation of cAMP pathways
. Inc. IGF-1 production in adipose
. IGF-1 greatly activates preadipocyte proliferation and differentiation of precursors into mature lipid-storing adipocytes
. Deficiency of GH assoc. w/ central obesity and replacement of GH dec. visceral adipocyte
Estrogens as endocrine signals to adipose tissue
. Lipoprotein lipase activity is inc. in gluteal-femoral region of women compared w/ more abdominal in men
. Treatment w/ estradiol inc. LPL in gluteal-femoral region
. Causes adipocyte precursor proliferation and regulating lipid storage in region-specific manner
Neutrals signals to adipose
. SubQ and visceral adipose have different rates of lipid synthesis and lipolysis reflecting differences in hormonal exposure and sympathetic innervation
. Catecholamines inc. lipolysis and inhibit adipose tissue hyperplasia from preadipocytes
Rate limiting steps of adipocyte lipolysis
. HSL and perilipin
. Both enzymes need to be phosphorylated to be active and allow the breakdown of triglycerides into glycerol and FFAs
Regulation of lipolysis
. Adrenergic systems (beta and alpha2 receptors) are major regulators of lipolysis via cAMP pathways
. Beta receptors stimulate lipolysis and alpha2 receptors inhibit lipolysis
.cAMP inc. activity of PKA that in turn phosphorylates the HSL and perilipin
. Insulin inhibits lipolysis via stimulate of phosphodiesterase (PDE) dec. cAMP and lipolysis
Adipose tissue hormones
. Sex steroids
. Lepton
. Wide variety of bioactive peptides (adipokines)
. Hormones act at local (autocrine/paracrine) and systemic (endocrine) level
. Affects energy homeostasis, insulin sensitivity, and nutrient-sensing pathways
Leptin
. Cross BBB and acts through different brain circuits to induce adaptive responses affecting appetite, energy expenditure, and neuroendocrine function
. Serves as metabolic signal of energy insufficiency
. Levels reduce w/ caloric restriction and weight loss
. Inc. in nutrient intake can inc. plasma leptin levels leading to activation of melanocortin receptors
. Results in dec. in glucose-stimulated insulin secretion
How leptin regulates neuroendocrine functions
. Dec. hypocortisolemia
. Inhibits stress-induced secretion of CRH
. Inhibits cortisol secretion from adrenocorical cells
. Normalizes reduced thyroid hormone levels in hypothyroid patients via TRH stimulation
. Accelerates puberty and restores normal gonadotropin secretion
Main biological function of leptin
. Maintenance of minimum level of energy stores during periods of caloric restriction
Leptin effect on immune response
. Contributes to regulation of immune response, hematopoietic, angiogenesis, bone development, and accelerates wound healing
How leptin seems to exert its peripheral metabolic effects
. Activates PKA in muscle and liver
. As consequence of PKA activation, ATP-consuming anabolic pathways are inhibited whereas ATP-producing catabolic pathways are activated
. Activated mechanisms include glucose transport, beta oxidation, glycolysis, and mitochondrial biogenesis
Adiponectin receptors
. AdipoR1: expressed primarily in mm.
. AdipoR2 express primarily in liver
. Biological effects of adiponectin depend on relative circulating conc. And properties of different adiponectin isoforms but also tissue-specific expression of adiponectin receptor subtypes
Adiponectin role in vasculature
. Binds to collagen types I, III, and V in vascular intima of injured vessels
. Role in vascular repair
Adiponectin relationship w/ body fat
. Concentration correlates neg. w/ BMI and body fat
. Inverse correlation w/ insulin resistance and obesity
Metabolic effects of adiponectin in liver
. Enhances insulin sensitivity, dec. influx of non-esterified FAs (NEFAs), inc. FA oxidation, reduces hepatic glucose output
