Transcript Pathways to obesity

The Cutting Edge: A Rumbling in the Belly
Microbiome: collectively all the microbes in the human body; a
community of microbes
Gut Microbiome: Two and a half to five pounds of normal or
gut flora (microbes) provide beneficial actions.
Each of us possesses a distinct bacterial enterotype—a personal
combination of different species of normal flora.
Gut flora perform regular tasks of digestion, vitamin production,
ferments simple carbohydrates, break down cellulose
The Cutting Edge: A Rumbling in the Belly
• Microbial genes turn on and off in response to what we
do (recall the lac operon?).
• Our genes turn on and off in response to what our
microbes do
• Gut–brain axis: how the microbiome influences anxiety
and depression
– Jane A. Foster ,Karen-Anne McVey Neufeld Trends in Neuroscience,
Volume 36, Issue 5, p305–312, May 2013
– microbiota are important in normal healthy brain function
– alterations in microbiota influence stress-related behaviors
The Cutting Edge: A Rumbling in the Belly
Interactions of microbes in the gut (intestine) early in life train
the immune system to distinguish self from non-self
(invaders).
microbes secrete compounds that regulate immune cells (T
cells) cytokines, chemokines which may prevent
pathogenic organisms from taking over
Some diseases and antibiotic treatments can drastically alter
the balance of our gut flora, resulting in pathogens being
able to become established.
Fecal transplantation is a treatment used effectively to
restore necessary gut flora.
Age Adjusted Obesity Rates
From CDC NHANES Study
Pathways to obesity
• Multiple factors
–
–
–
–
–
–
–
Overeating
Fat intake (“cafeteria” diet)
Alcohol intake
Inactivity (10% get regular exercise)
Metabolic issues
Genetics “Thrifty genome”
Combinations of above
• Overweight and obesity result from an energy imbalance
– Weight Gain:
Calories Consumed > Calories Used
– Weight Loss:
Calories Consumed < Calories Used
– No Weight Change:
Calories Consumed = Calories Used
Calories Used
• Physical activity is any bodily movement produced by skeletal
muscles that results in an expenditure of energy with a range of
activities such as
• Occupational work
Carpentry, construction work, waiting tables, farming
• Household chores
Washing floors or windows, gardening or yard work
• Leisure time activities
Walking, skating, biking, swimming, playing Frisbee, dancing
Structured sports or exercise Softball, tennis, football, aerobics
Eating Environment
• In America, a changing environment has broadened
food options and eating habits
– greater selection of products
– pre-packaged foods
– fast food restaurants
– soft drinks
• Portion size has also increased
Portion Distortion
In the last 50 years we’ve seen
–
–
–
–
–
…..
Plates
Drinks
Cup Holders
Servings
Ourselves
……..ALL GET LARGER!
Genetics
• “thrifty genotype” hypothesis : the same genes that
helped our ancestors survive occasional famines
– tendency to overeat
– tendency to be sedentary
– easily stimulated capacity to store body fat
• Evidence of genetic influence
– differences among family members, twins, and adoptees
– some genes at higher frequencies among the obese
• Many different genes contribute to the effects
– fat mass and obesity-associated gene might be responsible for
up to 22% of all cases
– gene for Leptin in rare cases
Genetics, Metabolic Rate, and Body Weight
• Genetics- heritability of .40 to .70 percent for obesity
• Metabolic
– Pima Indians who have an unusually high rate of
obesity
– This could be the FTO gene
• Fat mass and obesity-associated protein
– inked to a thrifty metabolism that allowed them to
metabolize food more efficiently
– variations in their mitochondrial DNA
Nutrient Regulation Helps Prepare for Future Needs
Energy expenditure is adjusted in response to nutrition.
At the start of a diet (less nutrition), the basal metabolic rate
will fall to prevent losing weight.
Restricted food intake promotes longevity, perhaps due to
trophic factors that promote cell growth.
Figure 13.19 Why Losing
Weight Is So Difficult
The Benefits of Caloric Restriction in Monkeys
Inherited Obesity: Both of these mice are (ob/ob)
•This mouse was treated with leptin
Leptin Treatment
Relation among weight, leptin, NPY, and eating.
0rdinarily, high levels of body fat produce leptin, which inhibits eating. Obese
mice fail to produce leptin. Obese humans produce leptin but fail to respond to it.
Obesity Treatments
– Dieting to reduce caloric intake
– Surgery
• Gastric stapling reduces stomach volume
– Compensation (stomach stretch after stapling)
• Intestinal bypass reduces food absorption
– Diarrhea and flatulence are problematic
– Bacterial overgrowth and vitamin deficiencies
– Pharmacological:
• Suppression of appetite
– Herbal preparations that that contain ephedrine
– Amphetamines or Cocaine
– Canabinoid antagonists producing an anti-high
• Blockade of fat absorption (Xenical)
• Drug effecting hypothalamus based on
– Leptin
– Ghrelin
– PYY
Body Fat Stores Are Tightly Regulated, Even
after Surgical Removal of Fat
Anorexia Nervosa & Bulimia
• Anorexia is the decreased sensation of appetite and can be
caused by many things such as emotional upset
• Anorexia nervosa
–
–
–
–
–
lack of desire to eat due to a mental disorder
an irrational fear of becoming obese
a preoccupation with their weight and food
a distorted body-image
persistently starve themselves and deny their appetites
• Bulimia
–
–
–
–
illness in which a person binges on food
has regular episodes of overeating
feels a loss of control
Various methods -- such as vomiting or laxative abuse -- to
prevent weight gain.
Fig 13.25
Facts and Stats
• Among normal weight female teens, 40-60% view themselves as
too heavy
• Up to 60% of female teens diet regularly
• Over 50% of teens exercise in order to improve their shape or lose
weight
• Approximately 45% of female teens smoke cigarettes to control
weight
• Most female teens are preoccupied with their food intake
• 70% of girls report that body shape is important to their self-esteem
(Strober and Schneider, 2005).
Social and Cultural Factors
•Controlling family members whom are often on diets
•perfectionists and overachievers
•“good” daughters who do what they’re told
•excel in everything they do
•focus on pleasing others
•Emphasis on physical appearance
•Participation in an activity that demands slenderness
•Ballet
•Gymnastics
•modeling
•Anxiety and/or Stressful events
•onset of puberty, a breakup, or going away to school
Genetic Factors May Predispose People to Eating Disorders
• Increased risk of anorexia nervosa among first-degree biological
relatives of individuals with the disorder
• Increased risk of mood disorders among first-degree biological
relatives of people with anorexia, particularly the bingeeating/purging type.
• Twin studies
– concordant rates for monozygotic twins is significantly higher than those for
dizygotic twins.
• Mothers who are overly concerned about their daughter’s weight
and physical attractiveness might cause increase risk for
development of eating disorders.
• Girls with eating disorders often have brothers and a father who are
overly critical of their weight.
Comorbidity
• Anorectics face an increased risk of depression, anxiety d/o
(especially OCD & Social Phobia), and personality d/o (cluster
C in anorectic restrictors; cluster B and C in anorectic
bulimics)
• Bulimics face an increased risk of depression; anxiety d/o may
also be increased
• The lifetime prevalence of substance abuse/dependence among
bulimics (particularly alcohol and stimulants) is at least 30%
(25% among all patients with an eating disorder)
• The diagnosis of a personality d/o among bulimics is not
uncommon (especially Borderline PD)