Energy Imbalances

Energy Imbalance

Overview of Obesity

  • Historical Context:
      - Obesity has been a long-standing issue within the human population.
      - Once considered rare, especially during times of famine.
      - Recent trend shows a drastic increase in obesity prevalence, particularly in the United States.
      - Within the last 40 years, rates have escalated from less than 15% to over 35%.
      - Notable increase in obesity observed in early life.

Efficiency of Energy Use

  • Basal Metabolic Rate (BMR) in Obese Subjects:
      - Obese individuals exhibit a more efficient BMR influenced by various factors.
      - Factors affecting BMR include:
        - Exercise
        - Age
        - Body temperature
        - Daily energy intake
        - Hormonal influences (e.g., ovulation, thyroid hormones, epinephrine, etc.)
      - Important premise: "A calorie is not always a calorie!"

Disrupted Signals in Energy Regulation

  • Anorexigenic vs. Orexigenic Signals:

    • Anorexigenic: signals that reduce appetite and promote the sensation of fullness, typically released by the body in response to adequate energy intake.

    • Orexigenic: signals that stimulate appetite and encourage food intake, often released during periods of energy deficit or starvation.
        - These signals work together to regulate appetite and energy balance.
        - Example hormones include leptin (anorexigenic) and ghrelin (orexigenic).
        - Reference:
          - J Clin Endocrinol Metab. 2012 Mar; 97(3): 745–755.

Leptin Deficiency / Resistance

  • Leptin's Role:
      - Leptin deficiency is rare in humans.
      - Research indicates levels:
        - Obese individuals: 31.3 ng leptin/ml
        - Lean individuals: 7.5 ng leptin/ml
      - Question arises: Why was leptin effective 40 years ago but not currently?

Mechanism of Leptin Resistance

  • Leptin Pathway:
      - Components involved:
        - Leptin binds to receptor LepRb, activating signaling pathway including JAK2 phosphorylation.
        - Involves various tyrosine phosphorylation sites (e.g., pY985, pY1077).
      - Negative Feedback:
        - Activation of inhibitory feedback loops involving SOCS3 and PTP1B.
        - In obesity, increased leptin levels correlate with reduced transport of leptin across the Blood-Brain Barrier (BBB) and impaired LepRb signaling due to inflammatory signals and ER stress.

  • High Leptin = Increased energy expenditure, but also leads to leptin resistance, which diminishes its effectiveness in regulating appetite and metabolism.

Energy Content of Foods

  • Global Sugar Supply:
      - Statistics from 2007 showed a breakdown of calories provided from sugar for different populations, highlighting trends leading to excessive caloric intake.

Glucose vs. Fructose

  • Blood Glucose Levels:
      - Variations in blood glucose levels observed during meals and their correlation with fructose intake to leptin and ghrelin influencing energy balance.

Signals in Central Nervous System Control of Energy Balance

  • Key Hormones:
      - Insulin, ghrelin, and leptin serve crucial roles in signaling satiety and controlling energy expenditure.
      - Effects of these hormones are modulated by food intake and body composition.

Hedonic Inputs Affecting Eating Behavior

  • Influencing Preferences:
      - Environmental (taste, appearance) and emotional factors significantly influence food intake.
      - Hormonal responses (e.g., insulin, leptin) dictate satiety signals in the system alongside nutrient availability.

Obesity as Energy Balance Disruption

  • Causes of Obesity:
      - Multifactorial aspects: lifestyle changes, food availability, and dietary composition (high-fat vs. high-sugar diets).
      - Obesity contributes to systemic inflammation, resulting in leptin and insulin resistance, perpetuating energy balance dysregulation.

Fasting and Starvation Adaptations

  • Physiological Responses:
      - Responses act as protective measures to sustain essential functions, favoring fat catabolism over glucose to reserve essential tissues.
      - Change to endogenous fuel utilization is immediate upon fasting onset.

Metabolism During Fasting

  • Stages of Blood Glucose Utilization:
      - Transition from exogenous glucose to endogenous sources like glycogen and gluconeogenesis in prolonged fasting states.

  • Energy Sources in Early Fasting:
      - Utilization patterns shift progressively through stored glycogen to initial lipolysis, entering a ketotic state after several days.

Hormonal Changes During Fasting

  • Hormonal Profiles:
      - Detailed changes in levels of insulin, glucagon, glucose, and fatty acids over various fasting conditions (very well fed, post-absorptive, fasted, and starved).

  • Altered Metabolism:
      - Observations reveal increased lipolysis, energy efficiency, and adaptation in amino acid usage with prolonged fasting.

  • Adaptive Thermogenesis:

    • This process involves adjustments in energy expenditure that help to conserve energy stores during extended periods of caloric restriction.


Caloric Restriction

  • Studies indicate that caloric restriction can lead to metabolic adaptations, enhancing lifespan and promoting cellular repair mechanisms.

Intermittent Fasting

  • Research has demonstrated that intermittent fasting can also trigger similar metabolic responses, improving insulin sensitivity and reducing inflammation.

Protein and Energy Malnutrition (PEM)

  • Marasmus:
      - Characterized by an overall lack of calories and protein, leading to wasting and loss of energy reserves.

  • Kwashiorkor:
      - Manifests from carbohydrate-sufficient but protein-deficient diets; results in preserved fat stores and muscle wasting, leading to edema and other physiological changes.