Williamson Obesity Flashcards
How is obesity generally defined?
Using BMI (body mass index = weight in kg / height in m).
What is obesity a consequence of?
Consuming more energy intake than your body needs through either too much food or too little exercise.
What are the main food categories?
Carbohydrates (sugars), fats, proteins, and fibre. We also need minerals and vitamins. Fibre is indigestible food material, mainly plant cellulose. No nutritive value – bulks up food and helps digestion and excretion.
What are characteristics of carbohydrates?
Historically, low fraction of European diet. Meat and fish have little. Fruit contains fructose and some sucrose. Milk contains lactose. Fruit and vegetables contain starch – harder to digest so released more slowly. Plant material contains lots of cellulose and hemicelluloses – not digested by humans. Main intake now is sweet food and sugary drinks – high content of refined sucrose.
What are characterisitcs in fats?
In meat and fish; and in seeds, hence vegetable oil etc. Many of the flavours we know and love are soluble in fat not water, so without fat, food has little taste. Fat also includes cholesterol.
In animals (and in humans) the main fat is triglycerides, and is stored in adipose tissue.
How do higher organisms store energy?
Animals store most of their energy reserves as fat. Plants store it as carbohydrates (starch). Not least because the energy content per gram is much greater in fats – so less weight to carry if it is fat. Plants don’t need to move! Sugars are water-soluble but fats aren’t, so sugars are much simpler to use.
How is protein catabolised?
Protein in food is needed for making protein. Needs breaking down to monomers, plus some recycling, and then build back up into protein. Stomach and gut contain a variety of enzymes to break proteins into amino acids and short peptides. Then transported into body: circulate in blood, and take up in tissue and liver.
How is fat catabolised?
Complicated because insoluble. Triacylglycerides in diet emulsified by bile salts, broken down by lipases and transported into mucus cells. Then reassembled into triacylglycerides and packaged into apolipoprotein-bound chylomicrons. The shorter chain fatty acids ( C14, more common in dairy products) do not need esterifying and are transported as free fatty acids (in chylomicrons etc).
How are lipids moved around the body?
Lipids pass into lymph system and then into the blood. When they reach target cells, they are broken down again. Subsequently either attached to CoA for -oxidation, or re-esterified for storage. Liver can oxidise fatty acids to ketone bodies which are soluble 4-carbon molecules and used eg by muscle.
How is sugar catabolised?
Body has very tightly controlled system for maintaining blood glucose constant, around 5 mM. Sugars in diet are broken down to monosaccharides in the gut, transported into epithelial gut cells, and then into blood. In the liver, different sugars are rapidly converted to glucose. Sugars taken up in diet are stored as glycogen (until no more space, and as long as insulin does its job). Prolonged excess glucose in diet messes up insulin control = type 2 diabetes. Excess sugars (ie peak in blood sugar or glycogen stores full) are converted to fat, via acetyl CoA.
What is the thrift gene hypothesis?
Short-term build-up of fat is good – but chronic nutritional excess is bad (positive selection for glucose and lipid metabolism genes – discussed in Bouchard 2007).
What energy sources do slow muscle fibres use?
In ‘slow’ muscle (non-skeletal muscle eg blood vessel contraction), most energy needs are met by conversion of glucose to pyruvate. This provides very little energy, but the advantage is that pyruvate is converted to lactate in muscle which is then recycled to the liver where it is converted back to glucose.
What energy sources does skeletal muscle use?
Skeletal muscle can use glucose or free fatty acids, or ketone bodies. ‘Fast twitch’ muscle almost entirely glucose from glycogen, because faster.
What tissues can only use glucose as an energy source?
One is red blood cells – no nucleus, no mitochondria, very little metabolism except glycolytic pathway. The other is the brain. If blood glucose drops below about 3 mM, the brain stops working and you go into a coma. (Brain can also use ketone bodies, though glucose is preferred.)
What happens to energy sources under starvation?
Fat can be converted to acetyl CoA and turned into ketone bodies which can keep most processes going. Except the brain, which needs some glucose – supplied by breaking down protein – very much a last resort as protein is never intended as an energy store. Breakdown of triacylglycerides also provides glycerol which can be converted to glucose
What are the different types of adipose tissue?
- white adipose tissue stores energy in fat. White adipose tissue (WAT) comprises up to 25% of body weight in healthy (non-obese) people (20% in men, 25% in women).
- brown adipose tissue contains lots of mitochondria – burns fats to regulate thermogenesis (‘non-shivering thermogenesis’). Animals that hibernate have lots of BAT. As humans age, the proportion of BAT decreases. BAT is probably much healthier because it takes fat from white adipose tissue and burns it. BAT usage is stimulated by low external temperature – so central heating could also be bad for us! BAT usage is also stimulated by fasting (eg EODF or every-other-day-fasting). Fasting also alters gut microbiota.
- Actually, BAT is a mixture of ‘true’ BAT, derived from myocyte precursor cells, plus beige adipose tissue derived from adipocyte precursor cells.
What stimulates brown adipose tissue activity?
BAT activity is stimulated by sirtuin. Sirtuin is a deacetylase – removes acetyl groups, eg on histones – and thereby changes gene regulation. Part of this regulates epigenetics.
Sirtuins are thought to be involved in response to starvation: they are upregulated during low calorie intake, and lead to enhanced beta-oxidation of fats and increased gluconeogenesis. In some way, sirtuins are thought to be important for the positive correlation between low calorie intake and longevity.
Other than being a fat store, what does adipose tissue do?
There is an acute rise in inflammatory mediators following a meal (next 4-8 hours). Greater in obese people. Inflammatory mediators generically called adipokines. They include interleukin-6 (IL-6) which is known to cause chronic ‘low grade’ inflammation.
bad. Adipose tissue also releases tumour necrosis factor α (TNF-α), another chronic inflammation signal, which also increases release of free fatty acids (FFA) from adipocytes. They also increase production of reactive oxygen species (ROS), which causes oxidative stress and endothelial dysfunction (eg reduction in NO release). This further increases risk of atherosclerosis.
What is leptin?
Another adipokine that reduces appetite. Different foods have different effects on inflammatory mediators released.
What are the links between inflammation and obesity?
Inflammation increases insulin resistance (especially when it happens at the same time as an increase in FFA). This leads to changes in lipid metabolism, eg higher LDL-cholesterol. Increases risk of atherosclerosis. Regulation of immune system gets worse with age. So chronic inflammation arising from obesity is likely to have more serious consequences as you age
What did GWAS show in terms of causes of obesity?
Shown strong association of obesity with a range of genes. Some of these regulate appetite, and some regulate metabolic control or physical activity. A high proportion of obesity is genetically linked. Twin and other genetic studies showed that 70% of obesity is genetically determined of which 40% are related to food intake.
Specifically, heritability is 70%, ie 70% of the variation in the population is due to genetic variation. This is not the same as inheritance. This does not mean you cannot control your fat, but it does mean it’s much easier for some people than others!
What does it mean if obesity if polygenic?
Lots of genes are involved not just one. This means that for the majority of obese people, the problem is a greater energy intake than in normal people.
What was the carbohydrate model for obesity (Ludwig et al)?
The “carbohydrate-insulin model” (Ludwig et al, 2021). Model suggests it is not as simple as energy intake vs energy expenditure. It focuses on the glycaemic load of your diet.
What is the glycaemic load?
= total carbohydrate x glycaemic index. Glycaemic index measures the increase in blood glucose after a meal. Therefore GL measures total increase in blood sugar, and therefore correlates with rise in insulin and decrease in glucagon. The effects of these hormones persist for several hours, and therefore affect how nutrients are metabolised and stored. They are also likely to affect the adipokine activity of adipose tissue, as discussed shortly.
