Ectopic lipids and non-alcoholic fatty liver disease(NAFLD) Flashcards
1
Q
What is ectopic fat?
What are the main types of fat storage?
A
- Fat (lipids) stored in places not designed for mass storage (i.e. not adipose tissue).
- Sites of fat storage:
1. Subcutaneous adipose tissue (ScAT) - located just under the layer of skin, safest/lowest CVD risk
2. Visceral adipose tissue (VAT) - deeper in abdomen, around organs associated with increased CVD risk
3. Intra-organ - stored within organs, associated with higher CVD risk
2&3 are classed as ectopic as it is only over a short time period
2
Q
How does the body adapt to low PA and increased sedentary behaviour?
A
- Body buffers excess energy by storing as adipocytes
- When finite capacity is reached, adipose tissue becomes dysfunctional, causes inflammatory reaction
- Insulin is important for metabolic homeostasis, cannot effectively uptake lipids into tissue (adipose tissue lipolysis) - increases breakdown of FFA
- Lipids then delivered to ectopic sites, e.g.: skeletal muscle which is involved in many metabolic diseases
- Hypoxia- when adiposities become starved of o2
3
Q
Describe how ectopic fat accumulates:
A
- increase energy intake/decrease energy expenditure
- increased: inflammation, hypoxia, proinflammatory cytokines, insulin resistance
- fat spill over (FFA) into liver, skeletal muscle, pancreas and heart
4
Q
What percentage of the population are likely to develop:
- Hepatic steatosis
- NASH(Non-alcoholic steatohepetitus)
- Cirrhosis
A
- 32%
- 10-30%
- 10-15%
- mainly related to obesity
5
Q
What is de novo lipogenesis?
What activates de novo lipogenesis?
A
- The formation of lipids in the liver from non-lipid precursors
- increased blood insulin & glucose
- glucose and fructose from the poor diet can both be used in DNL
6
Q
What are the 3 main supply roots for hepatic steatosis?
Describe the pathogenesis of hepatic steatosis:
A
- Dysfunctional adipose tissue
- TAG-rich chylomicrons
- insulin resistant skeletal muscle
- High dietary fat = increased lipolysis(in adipose tissue) –> more FFA in blood to be taken up by liver
- High fat could also be transported to liver by TAG chylomicrons for increased TAG synthesis
- High dietary fructose & glucose induce de novo lipogenesis = increased hepatic FFA
- also caused by skeletal muscle insulin resistance = more insulin to combat glucose in blood –> causing DNL
7
Q
Describe non-alcoholic fatty liver disease:
A
- Is the excessive storage of ectopic fat in the liver
- referred to as NAFLD when fat accumulation occurs in the absence of high alcohol consumption. - is fully reversible, strongly correlated with hepatic and whole body insulin resistance
- In obese people, the prevalence of NAFLD may be as high as 50–70%
8
Q
What body changes cause hepatic fat accumulation?
A
- NEFA plasma concentrations
- Lipid originating from a meal
- De novo lipogenesis (DNL)
- Hepatic export of VLDLs or
- Hepatic fat oxidation
9
Q
Describe NEFA:
A
- higher plasma NEFA concentrations (from elevated adipose tissue lipolysis) = higher hepatic NEFA influx = higher hepatic triacylglycerol (TAG) content
- Obese people with high intrahepatic lipid (IHL) content have a twofold higher rate of lipolysis than obese people with normal IHL content
- high fasting NEFA concentrations associated with obesity might contribute to elevated IHL content.
- impaired insulin suppresses lipolysis which may be an underlying factor in NAFLD
10
Q
How is NAFLD diagnosed?
A
- through a liver biopsy
- gold standard = visible lipid droplets in >5% of hepatocytes
- but is invasive and needs a specialist
- also through MRI, CT and blood biochemistry as they can detect inflammation
11
Q
What is the prevalence of NAFLD in the following populations:
- T2DM
- Obesity
- Severe obesity
A
- Currently affects ~32% of adults. Increased due to:
➢ Type 2 diabetes: ~60%
➢ Obesity (BMI ≥ 30kg/m2): ~70%
➢ Severe obesity (BMI ≥ 40kg/m2): >90% - Individuals with NAFLD are at a two-fold greater risk of developing T2D in the future. Shared mechanisms with insulin resistance
12
Q
What is the impact of NAFLD? What other metabolic diseases is it closely related to?
A
- T2DM
- cardiovascular disease
- insulin resistance
- dyslipidaemia - large quantities of lipid in the blood stream
- hypertension
13
Q
Define hepatic steatosis:
How does it develop?
A
- accumulation of liver fat
- Hepatic steatosis develops when lipid supply to the liver exceeds the ability to dispose of it.
- when supply(adipose tissue lipolysis, dietary fat & de novo lipogenesis) outweighs disposal(fat oxidation & VLDL-TAG export)
14
Q
What are the current mechanisms suggested to manage NAFLD?
A
- Lifestyle modifications, which include diet and physical activity to achieve weight loss, remain the first-line treatment for NAFLD.
15
Q
What are the 2 lifestyle modification guidelines for people with NAFLD?
A
- weight loss ≥ 5% total BM can reduce hepatic steatosis by ≥ 7% can lead to NASH resolution and ≥10% can result in fibrosis regression or stability –> more weight loss = greater benefit on physical health
- Regular physical activity for patients with NAFLD, (150-300 minutes of moderate-intensity) or (75-150 minutes of vigorous-intensity aerobic exercise per week).
➢ Resistance training can have independent beneficial effects on NAFLD.
➢ The impact of exercise on NAFLD can enhance the positive effect of a hypocaloric diet.
