The seventh and final lecture in the RuG Metabolism & Nutrition course was again delivered by Janine Kruit. This lecture tried to integrate the topics of the previous lectures, with the take-home message being that being obese is unhealthy.
In the pancreas, GLP-1 hormones, secreted by L cells in the small intestine, increase insulin secretion, insulin biosynthesis and β-cell proliferation and survival. In the brain, these same GLP-1 hormones signal satiety and cause a decrease in food intake and body weight. Also acting as a satiety signal, released from the small intestine to the brain, is CCK. There a more signalling peptides which act as satiation signals. (Ghrelin is an example of the opposite, an appetite-enhancing gastrointestinal peptide.)
Leptin is an adipokinese, a signal molecule from fat tissue. Leptin-defficient (ob-/ob-) mice and men never stop eating. Normally, a decrease in fat cell mass → decrease in leptin expression → decreasing leptin action in hypothalamus → increase in food intake, while an increase in fat cell mass → increase in leptin expression → increasing leptin action in hypothalamus → decrease in food intake. Obesitas causes leptin resistence, but it wasn’t clear from the lecture (or the slides) why…
Metabolic syndrome occurs when an excess of triacylglycerols can no longer be stored by the adipose tissue and is stored as lipid drops in other tissues. Insuline resistance results from energy stress (overnutrition and inactivity). Stress-induced serine kinases (which increase through the effects of mitochondrial overload and the increase of DAG and Ceramide) make GLUT4 less easily activated by the insuline receptor in the plasma membrane.
Blood glucose rises with insulin resistence, which makes the pancreatic beta-cells work harder to produce more insuline, until, finally, the pancreatic cells give in and Type II diabetes turns into Type I diabetes. During pregnancy, some measure insulin resistence is required. Maybe a contributing factor in insulin resistance is increased estrogen production by adipose tissues.
Metabolism during fasting
During fasting, the first priority is to keep blood [glucose] > 2.2 mM, to which end the liver mobilizes the glycogen store: Glycogen → G1-P → G6-P → Glucose. (In the muscles and brain, glycolysis produces pyruvate from G6-P. Pyruvate is burned into CO₂ and H₂O in the brain and in aerobically exercised muscle, and into lactate in anaerobically exercised muscle.) However, this is only enough for 1 day.
Gluconeogenesis uses amino acids to produce new glucose. Burning too much protein for energy is dangerous, though. The second priority is thus to maintain proteins. This is to some extent solved by ketone bodies [Fig 27.12/13], which can be formed from free fatty acids. Ketone bodies are hydrophilic and can pass the blood-brain barrier. Red blood cells still require glucose which is why the blood [glucose] has to remain > 2.2 mM.