Nutritional States and Systemic Disease

Introduction to Nutritional States and Systemic Disease

• Nutritional imbalances impact metabolism, inflammation, and organ function.
• Chronic conditions like diabetes, cardiovascular disease, and cancer are linked to dietary patterns and body composition.
• Obesity is a metabolic disease affecting the endocrine, cardiovascular, and immune systems.

Obesity

• A chronic disorder of energy regulation, characterized by excessive adipose tissue accumulation, contributing to metabolic dysfunction and increased disease risk.
• Childhood and adolescence are critical periods for establishing the total number of adipocytes or fat cells.
• Obese children and teens tend to have more adipocytes, which makes weight loss more difficult later in life.
• Weight gain in adults is primarily due to an increase in fat cell size (hypertrophy), not cell number.
• Central (visceral) obesity carries a higher risk of metabolic complications than peripheral (subcutaneous) fat.

Central Obesity and Associated Conditions

• Obesity is often associated with metabolic disorders.
• Insulin resistance and Type 2 diabetes arise due to chronic inflammation and altered hormone signaling.
• Dyslipidemia, marked by high triglycerides and low HDL, contributes to heart disease.
• Cardiovascular diseases linked to obesity include hypertension due to increased blood volume and vascular resistance.
• Atherosclerosis and heart disease are caused by a pro-inflammatory state and lipid imbalances.
• Liver complications include non-alcoholic fatty liver disease (NAFLD), where excess fat accumulation leads to fibrosis and cirrhosis.
• Respiratory disorders include obesity hypoventilation syndrome, where fat deposits restrict lung expansion, leading to hypoxia and sleep apnea.
• Musculoskeletal issues include osteoarthritis in weight-bearing joints due to chronic mechanical stress.
• Obesity increases the risk of colon, breast, endometrial, pancreatic, and liver cancers due to inflammation and hormonal changes.

Obesity Statistics

• By 2030, nearly 50% of American adults are projected to be obese.
• Approximately 25% of this group will have severe obesity (BMI ≥ 40).
• Obesity rates vary by region due to dietary habits, physical activity, socioeconomic factors, and genetics.
• Utah has lower obesity rates than the national average, possibly due to outdoor activity and healthier lifestyles.

Body Mass Index (BMI)

• BMI is a numerical measure of body fat based on weight and height.
• A normal BMI is between 18.5–24.9.
• Overweight is defined as a BMI of 25.0–29.9.
• Obese is defined as a BMI ≥ 30.
• BMI does not differentiate between fat and muscle mass and athletes may have high BMIs despite low body fat.
• BMI may not accurately reflect metabolic health and some individuals with "normal" BMI may still have metabolic syndrome due to visceral fat accumulation.

Fat Pathophysiologic Mechanisms

• Obesity results from an imbalance in energy intake vs. expenditure, regulated by neurohormonal pathways.

Three Main Components of Energy Regulation

• The three main components of energy regulation are Afferent signals, the central hypothalamic system, and the efferent system.
• Afferent signals are incoming signals to the brain.
• Insulin lowers appetite.
• Leptin signals satiety, but obesity leads to leptin resistance.
• Ghrelin increases appetite, and is known as the "hunger hormone."
• GLP-1 & Peptide YY promote satiety and reduce food intake.
• The hypothalamus integrates afferent signals and regulates hunger/satiety through neurotransmitters.
• The efferent system determines energy expenditure vs. fat storage based on neurohormonal feedback.
• Leptin lowers appetite.
• Ghrelin increases appetite.
• Peptide YY is a satiety hormone.

Energy Balance Circuitry

• The hypothalamus integrates signals to balance energy intake and expenditure.
• Anabolic circuitry promotes fat storage and appetite.
• Catabolic circuitry promotes energy expenditure and satiety.
• POMC & CART decrease appetite.
• NPY & AgRP increase appetite and decrease energy expenditure.

Obesity and Energy Balance Alterations

• More fat cells equals more leptin production, but in obesity, this does not effectively reduce appetite due to leptin resistance.
• Decreased adiponectin contributes to insulin resistance, diabetes, and fatty liver disease.
• Ghrelin levels do not decrease effectively after meals in obese individuals, leading to persistent hunger.

Obesity and Cancer

• Obesity increases the risk of multiple cancers, including breast, colon, and pancreatic cancer.
• Insulin stimulates insulin-like growth factor (IGF-1), which promotes cancer cell proliferation.
• Pro-inflammatory cytokines like TNF-α & IL-6 enhance tumor progression.
• Increased estrogen and androgens in obesity drive hormone-sensitive cancers like breast and endometrial cancer.

Adiponectin

• Adiponectin is protective against cancer, but its levels are reduced in obesity.
• Low adiponectin leads to reduced apoptosis and increased cell proliferation, making tumors more likely to form.

Diet and Cancer

• Exogenous carcinogens come from food and the environment.
• Animal fats and aflatoxin.
• Endogenous carcinogens are formed in the body.
• Nitrosamines are found in processed meats.
• Vitamins A, C, and E act as antioxidants and provide protection.
• Dietary fiber promotes gut health, reduces colon cancer risk by speeding up intestinal transit time.

Summary

• Obesity and cancer share common metabolic and inflammatory pathways.
• Hormonal dysregulation, chronic inflammation, and poor diet contribute to systemic disease progression.
• Lifestyle modifications like diet, exercise, and weight loss are crucial to reduce these risks.