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Metabolic Integration 2: Energy balance, the “diabesity” epidemic, biochemistry of nutrition and exercise Bioc 460 Spring 2008 - Lecture 41 (Miesfeld) Leptin is released from visceral fat and controls neuronal signaling in James Neel, M.D., proposed the term “thrifty gene” to explain the role of genes and lifestyle in “diabesity” Metformin

Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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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”. - PowerPoint PPT Presentation

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Page 1: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Metabolic Integration 2:Energy balance, the “diabesity” epidemic,

biochemistry of nutrition and exerciseBioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Leptin is released from visceral fat and

controls neuronal signaling in the brain

James Neel, M.D., proposed the term “thrifty gene” to

explain the role of genes and lifestyle in “diabesity”

Metformin

Page 2: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Metformin

Page 3: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

• 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.

Key Concepts in Metabolic Integration

Page 4: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

The “Diabesity” Epidemic

Page 5: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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.

Page 6: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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.

Page 7: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

The Thrifty Gene Hypothesis

Candidate genes may encode signaling proteins controlling metabolic homeostasis.

Overly active acetyl-CoA carboxylase?Maybe…

Increased sensitivity to insulin?Maybe…

What about increased levels of uncoupling protein for elevated thermogenesis?Very unlikely!

Page 8: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Leptin Controls Appetite and Energy Expenditure

The Obesity (Ob/Ob) All-Star Mice

Page 9: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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…...

Page 10: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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?

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?

Page 11: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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 over-stimulation of insulin signaling pathways, there is no response to insulin injections.

Glucose Tolerance Test

Page 12: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Metabolic link between obesity and diabetes

Page 13: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

In many cases, obesity leads to prediabetic symptoms that are characterized by elevated levels of serum glucose (hyperglycemia) and over-production of insulin (insulinaemia). If this condition persists, it will lead to insulin-resistance, and eventually, clinical type 2 diabetes.

Metabolic link between obesity and diabetes

Page 14: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Treatment of Type 2 Diabetes

Page 15: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Biochemistry of Nutrition and Exercise

The three primary factors influencing metabolic homeostasis are genetic

inheritance, nutrition, and exercise.

Page 16: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Strategies to Lose Weight

Page 17: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Most Diets Work About the Same in the End

Forty participants started on each diet, but 14-20 people dropped out. What does this tell you about the collateral effect of fad dieting?

Differences in weight loss and metabolic profiles were insignificant.

Page 18: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Good Calories and Bad Calories

What biochemical mechanism has been proposed to explain this observation?

Page 19: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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?

Page 20: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

You need to be in energy balance which requires only 1,800-2,200 Calories/day.

Page 21: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Biochemistry of Nutrition and Exercise

Page 22: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

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.

Page 23: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

AMPK Signaling is Activated by Exercise

Leads to increased levels of ATP

What two mechanisms turn off AMPK signaling when ATP needs are met?

Page 24: Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)

Extreme Sports and Final Exams

...maximize your potential energy!