Adipose tissue

Adipose tissue

1. Types of cells in adipose tissue

   • Fat cells
     • ~30-70% of total cell number
   • Stroma-vascular cells
     • Fibroblast
     • Macrophage
     • Mast cell
     • White blood cells
     • Adipose tissue derived stem cell (ADSC)
   • Specialised connective tissue

2. General function of adipose tissue

   • major energy store cells
     • virtually unlimited capacity
     • 40 days energy reserve in average person
     • Energy reserve
       • >80% as fat
       • 1% as CHO (glycogen/glucose)
   • Cushioning for internal organs
   • Insulation
   • Thermoregulation (BAT)
   • Act as a endocrine organ
     • Immune system
     • Regulation of feed intake
     • Insulin sensitivity
     • reproductive performance
   • Failure of adipose tissue
     • (1) Beradinelli-Seip syndrome
       • it is congenital先天性 generalised lipodystrophy
         • 'Lipodystrophy' defn
           • a condition of abnormal/ degenerative of body adipose tissue
       • cause
         • due to autosomal recessive condition
           • defn
             • a condition that requires two abnormal genes in order to develop the disease
           • lead to low levels of subcutaneous fat
       • Effect
         • Insulin resistance
           • Diabetes
         • Impaired fertility
         • Increase apetite
         • Ageing of skeletal system
         • Polycystic Ovary Syndrome
           • due to underdeveloped sac could not release egg,
             • hence no ovulation
     • (2) Cancer cachexia癌症恶病质
       • Effect
         • Loss of muscle mass
         • Loss of fat mass
           • due to poor outcomes in response to treatment
           • due to reduce food intake
           • increase energy expenditure
           • Tumour burden

3. Adiposegenesis

   • Origin
     • Mesenchymal stem cells
       • 2 pathways
         • Pathway 1: forms
           • Fibroblast
           • Myoblast
             • forms myocyte
           • Osteoblast
           • Chondroblast
           • • Wnt
         • Pathway 2 forms
           • i)Adipoblast -> preadipocyte
             • Hormones involved
               • Insulin
               • GF
               • IGF
               • T3
               • EGF
             • Pref-1
           • ii) Preadipocyte -> developing adipocytes
             • Within developing adipocytes, hormones involved:
               • Glucorticoid
               • T3
               • Insulin
               • IGF
             • W/in preadipocyte: induce autocrine; C/EBPβ
             • Within developing adipocytes: induce autocrin; such as
               • C/EBPα
               • PPARγ2
               • ADD1
           • iii) Developing adipocytes -> mature adipocytes
           • Transcription invovled
             • Bone Morphogenic proteins (BMPs)
             • Schnurri-2
       • Transcription factors involved
         • BMPs
         • Hedgehog

4. Types of adipose tissue

   • White adipose tissue (WAT)
     • Differentiation
       • Mesenchymal stem cell -> adipoblast (Myf5- precursor)
         • Adipoblast -> white preadipocytes
           • White adipocytes
     • Defn
       • is a lipid storage that has a few mitochondria and made up of unilocular droplet
         • unilocular droplet, i.e. TAG
     • Funtion
       • Energy storage
       • Endocrine function
     • Found in
       • subcutaneous
       • Abdominal
       • Intra-abdominal
       • Other sites (refer to iphone)
     • Basic concept
       • Adipocytes hypertrophy (increases in size) in response to over-nutrition
       • When lipid oversupply:
         • Lipid accumulation in other tissues
           • Liver
           • Muscle
       • nucleus locate on periphery 外圍of the cell
       • mitochondria found in WAT are more efficient
         • Why?
           • Coupling occurs; oxidative phosphorylation
             • H+ binds with ATP synthase at mitochondrial inner membrane
               • synthesis of ATP
       • White and Brown adipocyte interconversion ??
         • Developed in different lineages
           • therefore not exactly a interconversion
             • but hybrid-like 混合類 adipocyte; brite adipocyte
               • it is converted from white adipocytes
               • increase energy expenditure
   • Brown adipose tissue (BAT)
     • Differentiation
       • Mesenchymal stem cell -> adipoblast (Mfy5+)
         • Adipoblast -> Brown preadipocyte
           • Brown adipocyte
     • Defn
       • A thermogenic tissue that has a large number of mitochondria
     • Function
       • generate heat
         • Due to UCP-1 in...
           • Mitochondria
           • multilocular lipid droplets
     • Found in
       • Cervical
       • Suprcalvicular
       • Paravertebral
       • Interscapular
     • Basic concenpts
       • more cytoplasm than WAT
       • more "inefficient" mitochondria
         • Why inefficient?
           • oppose the production of ATP
           • instead w/in mitochondrial inner membrane, proton leak
             • cause uncoupling
               • UCP-1 produces heat
                 • important in non-shivering thermogenesis
                 • Initiation of UCP-1
                   • Due to enviromental factors
                     • i.e. cold / diet
                     • stimulates sympathetic nervous system
                       • Signals brown adipocyte via beta3
                         • beta3
                           • triggers cAMP to induce messeage PKA
                             • PKA causes UCP-1 to increase
                               • heat generation
       • nucleus at centre of cells
       • Low abundance
       • Multiple lipid droplets w/in a cells
       • BAT are observed in neonates (baby)
         • Why? maintain core body temp
         • low amount of BAT in adults
           • prolong exposure to cold increases BAT
             • however, effect not seen in obese ppl
         • High abundant in adult rodents

5. Basic concepts

   • No. of adipocytes can increase in childhood
     • BUT remains stable in adulthood

6. Risk of excess visceral fat

   • Biological impact
     • (1) Hypertriglycemia
     • (2) High apolipoprotein B
     • (3) Low HDL
     • (4) Inflammation
     • (5) Insulin resistance
     • (6) Hyperinsulinaemia
     • (7) Endothelial dysfunction
     • Can lead to:
       • Type 2 diabetes
       • Metabolic disease
       • Cardiovascular disease