Metabolic Integration 2: Energy balance, the

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Metabolic Integration 2Energy balance, the
diabesity epidemic, biochemistry of nutrition
and exercise
Bioc 460 Spring 2008 - Lecture 41 (Miesfeld)
Metformin
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
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Metformin
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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.

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The Diabesity Epidemic
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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.
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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.
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The Thrifty Gene Hypothesis
Overly active acetyl-CoA carboxylase? Maybe Incr
eased 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.
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Leptin Controls Appetite and Energy Expenditure
The Obesity (Ob/Ob) All-Star Mice
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Leptin may be a type of fat-o-stat
You are battling against built-in biochemical
processes that make sure you dont lose valuable
fuel. The opposite should also be true, so push
away from the table when you feel full...
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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?
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Glucose Tolerance Test
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.
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Metabolic link between obesity and diabetes
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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
over-production of insulin (insulinaemia). If
this condition persists, it will lead to
insulin-resistance, and eventually, clinical type
2 diabetes.
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Treatment of Type 2 Diabetes
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Biochemistry of Nutrition and Exercise
The three primary factors influencing metabolic
homeostasis are genetic inheritance, nutrition,
and exercise.
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Strategies to Lose Weight
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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?
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Good Calories and Bad Calories
What biochemical mechanism has been proposed to
explain this observation?
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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?
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You need to be in energy balance which requires
only 1,800-2,200 Calories/day.
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Biochemistry of Nutrition and Exercise
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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.
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AMPK Signaling is Activated by Exercise
What two mechanisms turn off AMPK signaling when
ATP needs are met?
Leads to increased levels of ATP
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Extreme Sports and Final Exams
...maximize your potential energy!