adipose tissue remodelling

Question 1

obesity

Answer 1

recognised as one of the most important public health challenges
global obesity prevalence in adults has risen by 2% per decade, currently stands at 13%
small increases in obesity prevalence means millions more people having obesity related diseases
why- primary cause is positive energy balance disrupting energy homeostasis
initial fat accumalates in white adipose tissue and subsequently in other tissues

Question 2

adipose tissue

Answer 2

comprised of various cell types including mature adipocytes, stromal cells, fibroblasts, macrophages, blood cells, endothelial cells, smooth muscle cells, mesenchymal stem cells and adipocyte pre cursor cells
can cope with excess energy in 2 ways:
- hyperplasia- more cells, occurs through differentiation and proliferation of adipose precursor cells
- hypertrophy- larger cells increase in exisiting adipocyte size
-

Question 3

hyperplasia

Answer 3

increase in the number of cells in organ/tissue
mesenchymal stem cells are multipotent - differentiate into many cells
an event occurs eg positive energy balance that causes signalling factors that cause some MSCs to commit to becoming APCs
these APCs differentiate and can form brown adipocytes or white adipocytes
hyperplasia in specific fat depot is primarily established in early life and tends to remain stable throughout life (genetically determined)

Question 4

adipose depots

Answer 4

subcutaneous adipose tissue
visceral adipose tissue

Question 5

hyperplasia- sex

Answer 5

female- oestrogen impacts appetite, caloric intake and energy expenditure- promotes subcutaneous fat accumlation particularly in gluto femoral eegion, resulting in pear shaped female body

male- testosterone favours the deposition of visceral fat, leading to apple shaped male body

Question 6

hyperplasia + hypertrophy- age

Answer 6

0-2 years- rapid hypeplasia and hypertrophy
12-18- continued rapid both
adulthood- hyperplasia declines/ stabilises, continued rapid hypertrophy, particularly in visceral depots

Question 7

hyperplasia age explained

Answer 7

rapid increase in pre adulthood occurs particularly in subcutaneous adipose tissue due to rapid growth hormone, IGF- 1, sex steroids anf nutritiional factors
childhood obesity characterised by acclerated adipose tissue hyperplasia

Question 8

adipose tissue hyperplasia with obesity

Answer 8

weight stable condition (normal) - 10% annual turonover of adipocytes involving a tightly regulated balance of adipogenesis and adipocyte death
over nutrition (obese)- adipose hyperplasia and increased mass,
- animal models suggest genetic involvement- regulation of hyperplasia by leptin (supresses hunger) plays a large role

Question 9

adipose hyperplasia- restructrure

Answer 9

replacement of mature adipocyte is acarried out by APC priliferation to new adipocytes, supported by proliferation of other stromal cells to ensure sufficient blood flow to supply oxygen and other nutritents to growing tissue

Question 10

adipose hyperplasia- number and size

Answer 10

critical to metabolic health; many smaller adipocytes characterised better metabolic status, expressed by higher insulin sensitivity, lower inflammation and less ectopic lipid accumalation

Question 11

regulators of adipose tissue hyperplasia

Answer 11

centrally- hormones and cytokines regulate satiety/hunger, metabolic and activity states in a complex net of interactions
major central regulators include glucagon peptide 1, neuropeptide Y, leptin, ghrelin and CKK
peripherally- molecular regulators of adipose cell number include insulin, retinoids, corticosteroids and tumour necrosis factor alpha (TNF-a)

Question 12

hypertrophy

Answer 12

increases adiposity, insulin resistance and inflammation
decreased adipose tissue function
adipose distribution- less subcutenaous fat and more visceral fat
lipid storage- decreased lipid storage capacity, increased in liver and skeletal muscle

Question 13

adipocyte hypertrophy obesity

Answer 13

occurs most post developmentally in response to over nutrition, is depdendent on the capacity of exisiting adipocytes to capture and retain circulating lipids
during caloric restriction, adipocytes provide nutrients to other tissues through stored lipids and the release of FFAs into circulation
adipose tissue hypertrophy with obesity is complex phenomenom expressed by the increase in size of the individual’s cells and remodelling of adipose tissue

Question 14

characteristics of hypertrophy

Answer 14

is pro inflammatory
hypoxic- poor vascular expansion as adipocytes expand
dead adipocytes
fibrosis occurs- thickening/scarring
insulin resistant tissue
diminished capacity to store fat

Question 15

adipose tissue overflow

Answer 15

in responsive state- hypertrophy can reach a plateau that triggers the generation of new adipocytes to accumalate excess fat and reduce spill over to other tissues
in contrast, states of extreme hypertrophic obesity are characterised by reduced hyperplasia and further hypertrophic expansion, accelrating risk of co morbidites
enlarged fat cells have diminished capacity to store fat
meaning fat spill over is directed to non adipose tissue - skeletal muscle, liver and pancreas- whcih accumalte excess toxic fatty acids

Question 16

triglyceride accumalation

Answer 16

harms cells and causes cell malfunction due to the activation of inflammatory and stress response pathways - lipotoxicity- and contributes to obesity comoorbidity eitlogy

Question 17

south asian CVD paradox

Answer 17

applies research area
heterogenous group comprising ~25% of global population but account for 60% of heart disease patients
largest ethnic minority in UK
all migrant SA populations have elevated risk of CVD compared to other ethnicities
smoking rates, alcohol usage, hypertension, BMI, cholesterol may play a role
CV risk assessment (UK SAs)- 92% had 1 modifiable risk factor- 40% were obese + 75% had central adiposity

Question 18

importance of body fat

Answer 18

originally considered to be a simple storage organ for lipids- but not the vase
adipose tissue is an endocrine organ responsible for the synthesis and secretion of several hormones
adipose tissue is not uniform, depending on location it differs in capacity to secrete adipokines

Question 19

distribution of body fat

Answer 19

very important
- superficial- tightly packed organised lobules, relatively benign
- deep subcutaneous adipose tissue, larger irregular lobules, related to metbolic dysfunction
- visceral/ intra abdomial adipose tissue- samllest but often linked to metabolic complications

Question 20

related to ethnicity

Answer 20

adipose tissue overflow hypothesis
1. adipocytes expand and new adipocytes are formed
2. south asians have reduced capcity for adipocyte hyperplasia and therefore reduced capcity to store fat in superficial adipose tissue
3. fat spills over into secondary comparetments
4. explains why for any given BMI, south asians have higher WHR and higher disease risk to white people

Question 21

chronic inflammation

Answer 21

linked to insulin reisstance, endothelial dysfynction, imapred lipid homeostasis
30% circulating IL-6 originates from adipose tissue, concentrations are higher in visceral fat, concentrations increase with obesity
adipocytes are source of TNF-a, IL-6 and TNF-a associated with mortality
CRP is an acute phase protein, is mainly priduced in liver in response to IL6, CRP is a strong predictor of CVD

Question 22

immune cell infiltration

Answer 22

Infiltrating immune cells not only produce cytokines but also metalloproteinases, reactive oxygen species, and chemokines that participate in tissue remodelling, cell signalling, and regulation of immunity