body composition and adipose tissue

changes in body size with age

decreased weight in older ages

waist circumference increases

examples and magnitude of changes in body size

Health Survey for England, 2021: decreased height, -7.7cm in males, -6.6cm in females

Health Survey for England 2013: Max weight when middle aged (45-54 y/o), then decrease

HSE 2021: increased mean BMI up to 45-54 in males then decreases minorly, increases up to 74 in women then decreases

changes in body composition with age

fat free mass declines consistently with age

BMI is highest at middle-aged

fat mass declines at most advanced ages

examples and magnitude of changes in body compostion

Ding 2007

later birth cohorts had a higher FM and LM

males have more LM and less FM compared to females

Spirduso: Waist: Hip ratio

possible consequences of changes

increased risk of many diseases including CVD

low fat-free mass and high waist circumference are more predictive of mortality

higher mortality

body composition

fat and muscle vary between individuals

females have highest proportion of fat

males have highest proportion of muscles

BMI

• Body mass index: weight (kg)/height (m)2​

• Measure of weight for height​

• BUT- may be elevated by increased fat or lean

Fat mass

• Fat mass​

• Chemically defined fat, including essential fat​

• Can be expressed as FMI: FM/height2

Fat-free mass

Fat-free mass​

• Everything else: Viscera, muscle, skin, bone etc​

• Can be expressed as FFMI: FFM/height2

body composition assessment

Imaging​

• DXA​

• MRI​

• CT​

Densitometry​

• Underwater weighing​

• Bodpod​

Total Body Water by isotope dilution​

Biolectrical impedance analysis (BIA)​

Anthropometry e.g. skinfolds​

BMI​

pathophysiology of obesity

• excessive fat and adipose tissue which could be caused by diet, leading to disorders in adipose tissue

• physical and metabolic effects

• adipose tissue expansion

mortality cause

higher risk of cancer, CVD and other causes with an elevated BMI

FFM may be more important than FM in older people

preclinical obesity

minor or absent clinical manifestations

clinical obesity

complications, end-organ damage

may include problems in CNS, renal, reproductive, respiratory, limitations in physical activity

mean weight according to age

increases to around 45-54 years old then gradually decreases with age

mean BMI by age

increases up to 45-54 in males then decreases minorly

increases up to 74 in women then decreases

birth cohort

consistent decline in lean mass with age

reduction in fat mass with age, less consistent than lean mass

increased fat/lean mass in later birth years

less lean and fat mass in females

waist:hip

spirduso

males: apple shaped, increase from 30-50 years by 0.09

females: pear shaped, increase from 30-50 years by 0.1

optimal fatness

Optimal BMI for lowest mortality at age 65+ overweight to mildly obese (25-35 kg/m2)​

BMI may be affected by:​

• Loss of lean tissue​

• Height loss​

Strongest predictors of mortality in older people include:​

• Waist circumference ​

• Low lean body mass​

• Optimal %fat 24.1-29.4 for men; 42.5-46.4 for women​

​Chang (2012)

white adipose tissue

energy storage, thermal insulation, mechanical protection, endocrine organ

releases hormones, cytokines, lipids, enzymes e.g. lipoprotein, lipase

brown adipose tissue function and assessment

thermogenesis

endocrine organ

Beta-adrenergic signalling activates tissue-specific uncoupling protein 1 (UCP-1) ​

• Allows protons to return to mitochondrial matrix, reducing electrochemical gradient​

• Releases heat

• Assessed by positron emission tomography CT or MRI​

• Located in neck, shoulders, posterior thorax, abdomen​

• Warmed blood drains directly to systemic circulation ​

• Secretes ​bioactive lipids (e.g. 12-13-diHOME) that stimulate glucose and fatty acid uptake​, microRNAs that affect gene expression e.g. in liver​

• May lower risk of atherosclerosis; improve insulin sensitivity; resistant to inflammation​

prevalence decreases at high temperatures

higher prevalence with low BMI

declines with age

bone marrow adipose tissue

Bone marrow houses:​

• Stem cell populations​

• Hematopoietic stem cells​

• give rise to blood cells​

• Mesenchymal stem cells​

• can differentiate into a variety ofcell types: adipocytes,osteoblasts, chondrocytes etc​

• Adipose tissue (white)​

• Blood vessels​

changes in adipose tissue with age

increase in obesity prevalence and high waist circumference to middle aged, which then decreases but increases in women waist circumference

less subcutaneous fat, more visceral fat

relationship between adipose tissue distribution with disease risk and mortality

Within a weight category, those with higher WHR had higher risk of hypertension and diabetes

Normal weight, WHR>0.8 had same diabetes risk as >50% overweight , WHR<0.73

Highest weight and WHR had ~10x diabetes risk of lowest groups

higher risk for total mortality, CVD and cancer mortality with a high WHR and high BMI

high risk for CVD mortality with a low BMI and high WHR

visceral fat and metabolic syndrome

mechanisms that mediate associations

reduced ability to store fat subcutaneously-reduced skinfold thickness and hip circumference

greater proportion of fat stored viscerally-increased waist circumference, adverse health outcomes

inactivity

endocrine changes: decline in sex steroids, increased cortisol, decline in GH axis, leptin resistance

beige adipose tissue

cold and adrenergic stimulation leads to a transition from white-like to brown-like functions

adipocytes

secretes hormones:

Leptin​

Adiponectin​

• Regulates glucose metabolism, increases insulin sensitivity​

• Regulates lipid metabolism to reduce atherogenesis​

• Anti-inflammatory​

Oestrogen​

cytokines

fatty acids

leptin

• Low leptin signals low energy and starvation​

• Leptin suppresses appetite, but leptin resistance can develop in obesity​

adiponectin

• Regulates glucose metabolism, increases insulin sensitivity​

• Regulates lipid metabolism to reduce atherogenesis​

• Anti-inflammatory​

oestrogen

Conversion from androgens by enzyme aromatase​

white adipocytes

Constant turnover- replaced over 15y​

Adipose tissue volume can increase by:​

• Hypertrophy from 30mm to >100 mm​

• Or hyperplasia- increase in cell number​

Obesity can impair preadipocyte differentiation​

• Increases hypertrophy​

• Reduced insulin signalling and glucose uptake​

• Reduced adiponectin release​

• Limited possibility for oxygen diffusion from capillaries​- Increased inflammation and cell damage​

Limited expansion leads to overflow​

• Ectopic fat- liver and skeletal muscle​

• Contributes to immune dysfunction, atherosclerosis, insulinresistance etc​

obesity

can impair preadipocyte differentiation

increases hypertrophy

reduced insulin signalling and glucose uptake

reduced adiponectin uptake

limited possibility for O2 diffusion from capillaries

complications of obesity

neuropsychological: stroke, cataracts, depression

pulmonary: pulmonary embolism

gastrointestinal: gallbladder disease, pancreatic

endocrine; type 2 diabetes

reproductive: abnormal menses, infertility, male hypogonadism

oncologic: breast/ovary/uterus/oesophagus/stomach/colon cancer, multiple myeloma

immunologic: chronic inflammation, susceptibility to infection

cardiovascular: CVD, hypertension, thrombosis, edema

musculoskeletal: lower back pain, osteoarthritis

adipose tissue depots

subcutaneous and visceral

visceral-inside abdominal/thoracic cavity

ectopic fat accumulation in organs

measure of fat distribution

• MRI or CT scan​

• Waist circumference​

• Waist to hip circumference ratio (WHR)

metabolic syndrome

• Abdominal obesity, given as waist circumference​

• Men >102 cm (40 in)​

• Women >88 cm (35 in)​

• Triglycerides >150 mg/dL​

• HDL cholesterol​

• Men <40 mg/dL​

• Women <50 mg/dL​

• Blood pressure >130/85 mm Hg​

• Fasting glucose >110 mg/dL​

visceral fat

• More metabolically active​

• Greater response to sympathetic stimulation​

• Releases fatty acids into portal vein​

• Increased hepatic production LDL ​

• Increased gluconeogenesis​

• Less leptin production​

• ​Wong 2003

fat accumulation in organs

Greater fat accumulation in other organs with age (generally relatedto abdominal fat content)​

• Liver​

• Increased fat content with age seen in some but not all studies​

• Fatty liver associated with impaired glucose metabolism, increased gluconeogenesis, hyperinsulinaemia; dyslipidaemia; hypertension​

Inter- and Intra-muscular​

• Bone marrow​

• Associated with osteoporosis and osteoarthritis​

Epicardially​

• Associated with ventricular hypertrophy, inflammatory markers and increased risk of coronary artery disease​

Intra-myocardial​

assessing bone marrow

iliac crest biopsy

MRI showing fat signal image

MR spectroscopy

heamatopoetic cellularity with age

declines rapidly with age in tibia and femur at ~30-distal sites

declines in rib, sternum and vertebra around 40 y/o/

changes in marrow composition with age

Lumbar spine adiposity (% of marrow volume) according to MRI in cross-sectional studies​

• 20-30% at age 20​

• ~50% at age 50​

• ~60% at age 80 in men​

• >70% at age 80 in women​

Femur adiposity​

• Femoral shaft increases from 60% adipose in 20s to 80% in 60s​

• Femoral head increases from 80% adipose in 20s to 90% in 60s​

Marrow adiposity increases at menopause and decreases with oestrogen supplementation​

Marrow adiposity increases with caloric restriction!​

bone marrow adipocytes

• Like peripheral adipocytes,store fat and energy, secreteadipokines and cytokines andexpress insulin receptor​

• FFAs provide energy for boneformation, neoplastic growth,haematopoiesis​

• Unlike peripheral adipocytes,secrete signalling mediatorssuch as RANKL that affectcell metabolism andtranscription and growthfactors ​

• Rodent studies suggests bone marrow is a major source of adiponectin, particularly in caloric restriction​