Metabolic Integration 2: Energy balance, the “diabesity” epidemic, biochemistry of nutrition and exercise Bioc 460 Spring 2008 - Lecture 41 (Miesfeld) Metformin James Neel, M.D., proposed the term “thrifty gene” to explain the role of genes and lifestyle in “diabesity” Leptin is released from visceral fat and controls neuronal signaling in the brain Metformin Key Concepts in Metabolic Integration • Energy balance refers to the metabolic state in which the Calories contained in the metabolic fuel you consume are equal to the Calories you expend. • Leptin is a peptide hormone that is secreted by visceral adipose tissue in proportion to the amount of stored lipid. • Choosing oils that low in saturated fats, and carbohydrates with a low glycemic index, can add value to your food. • Studies have suggested that regular moderate to intense physical exercise can stimulate signaling pathways in muscle cells. The “Diabesity” Epidemic Metabolic Energy Balance Being in energy balance just means your weight is staying the same, it does not mean you are at a healthy weight. The Thrifty Gene Hypothesis James Neel proposed a thrifty gene hypothesis to explain the genetic basis for obesity and diabetes in modern times. It should be reversible. Pima Indians of Mexico weigh on average 57 pounds less than their Arizona relatives and the incidence of diabetes is almost nine times lower. The Thrifty Gene Hypothesis Overly active acetyl-CoA carboxylase? Maybe… Increased sensitivity to insulin? Maybe… What about increased levels of uncoupling protein for elevated thermogenesis? Very unlikely! Candidate genes may encode signaling proteins controlling metabolic homeostasis. Leptin Controls Appetite and Energy Expenditure The Obesity (Ob/Ob) All-Star Mice Leptin may be a type of “fat-o-stat” You are battling against built-in biochemical processes that make sure you don’t lose valuable fuel. The opposite should also be true, so push away from the table when you feel full…... Why does it make sense that leptin and insulin have the same effect on neuronal signaling, what signal are they each sending to the brain? Based on the function and localized secretion of ghrelin and PYY3-36, why is it good advice to eat slowly if you are trying to lose weight? Metabolic link between obesity and type 2 diabetes Type 1 diabetes is due to loss of insulin production, usually as a result of pancreatic cell death. Insulin treatment works well. Type 2 diabetes is the result of chronic overstimulation of insulin signaling pathways, there is no response to insulin injections. Glucose Tolerance Test Metabolic link between obesity and diabetes Metabolic link between obesity and diabetes In many cases, obesity leads to prediabetic symptoms that are characterized by elevated levels of serum glucose (hyperglycemia) and overproduction of insulin (insulinaemia). If this condition persists, it will lead to insulin-resistance, and eventually, clinical type 2 diabetes. Treatment of Type 2 Diabetes Biochemistry of Nutrition and Exercise The three primary factors influencing metabolic homeostasis are genetic inheritance, nutrition, and exercise. Strategies to Lose Weight Most Diets Work About the Same in the End Differences in weight loss and metabolic profiles were insignificant. Forty participants started on each diet, but 14-20 people dropped out. What does this tell you about the collateral effect of fad dieting? Good Calories and Bad Calories What biochemical mechanism has been proposed to explain this observation? Good Calories and Bad Calories The glycemic index (GI) is a numerical value that indicates how quickly glucose is released into the blood after eating different types of carbohydrate-containing foods. Why are low glycemic index foods thought to be better for you? You need to be in energy balance which requires only 1,800-2,200 Calories/day. Biochemistry of Nutrition and Exercise Exercise is Beneficial Even Without Weight Loss Group 1 did not exercise at all, group 2 performed exercise three times a week at moderate intensity, and group 3 performed the same exercise regimen but at high intensity. Group 3 had the biggest metabolic benefit. AMPK Signaling is Activated by Exercise What two mechanisms turn off AMPK signaling when ATP needs are met? Leads to increased levels of ATP Extreme Sports and Final Exams ...maximize your potential energy!