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!