Type 2 diabetes Pt 2 Flashcards
Free Fatty acids and glycerol in the blood:
- Don’t forget the dysfunctional adipocyte loses lipid droplets and goes into the blood
- The body can either use it or excrete it
- Plus the dietary lipids from meals are not being stored properly
- The body has ectopic lipid accumulation and lipotoxicity to deal with this issue
Lipotoxicity
- excessive lipids in the blood that can be toxic to cells
- Excessive blood lipids are from DIET, UNCONTROLLED LIPOLYSIS, AND LIVER LIPOGENESIS (producing lipids because it’s in the fasted state)
PROOF OF REVERSE LIPOTOXICITY
- The mice were given an HFD and suffered from lipid toxicity. Once the serum lipid is transplanted the visceral fat becomes subcutaneous fat. Reduces fat in the blood
Where does the excess lipid go?
- The liver thinks it can function like adipose tissue and take up lipids. This starts the progression of nonalcoholic fatty liver disease
- Nonalcoholic fatty liver disease: hepatocytes store the huge lipid droplet
Normal Liver Function
- Two main lobes: hepatic artery, oxygen-rich, and portal vein, nutrient-rich blood
- 8 segments connected to the hepatic duct transporting bile
- All blood leaving the stomach and intestines passes through the liver
- Processes and breakdown of nutrients
- Metabolizes drugs and toxins
3 cell types in Liver
Hepatocyte, Stellate Cells, and Kupffer Cells
Sinusoid
fenestrated capillary, a mix of oxygen and nutrients to flow around the body
Hepatocyte
: manufacture many proteins, enzymes, lipids, and cholesterol that are utilized in the body
Stellate Cells
liver-specific mesenchymal cells(in connective tissues) . Contains numerous vitamin A lipid droplets, the largest reservoirs of vitamin A in the body.
Kupffer Cells:
specialized macrophages located in the liver lining the walls of the sinusoids. Bad circumstances can lead to fibrosis.
Major Metabolic Role of Liver:
- Detoxify
- Glucose metabolism and production
- Lipid synthesis and secretion
Gluconeogenesis
- Requires: glycerol and free fatty acids coming from adipocyte triglyceride lipolysis
- Cori cycle: glucose to pyruvate (muscle) to locate which makes back pyruvate(liver) and then glucose. Muscle using glucose
- These are important because Gluconeogenesis adds glucose to the blood promoting hyperglycemia. Cori provides the substrate for Gluconeogenesis because the muscle is in an insulin-resistant state
Difference between NAFLD and NAFL and NASH:
- NAFL: absence of inflammation and the damage is benign
- NAFLD: spectrum of liver conditions. Hepatic triglyceride accumulation
- NASH nonalcoholic steatohepatitis: the presence of both lobular inflammation (Kupffer cells involved) and hepatocellular
- Cirrhosis-fibrosis progression of NAFLD and NASH: hepatocellular carcinoma (liver cancer) For Fibrosis it’s the deposits of collagen that ruin the tissue function
Two paths of NAFLD:
- Nonprogressive remains NAFL. More protective and unlikely to develop fibrosis
- Progressive advance rapidly to NASH and fibrosis
- No one really understands why some remain nonprogressive, genetic diet
Where do lipids come from?
Where do lipids come from?
60% hepatic fatty acids from adipose tissue
25% de novo lipogenesis
15% from diet