Metabolic Syndrome, Diet, and Immune Function PDF

METABOLIC SYNDROME, DIET, AND IMMUNITY METABOLIC SYNDROME ▪ “Metabolic" refers to the biochemical processes involved in the body's normal functioning. ▪ “Metabolic syndrome” a cluster of biochemical and physiological abnormalities associated with the development...

METABOLIC SYNDROME, DIET, AND IMMUNITY METABOLIC SYNDROME ▪ “Metabolic" refers to the biochemical processes involved in the body's normal functioning. ▪ “Metabolic syndrome” a cluster of biochemical and physiological abnormalities associated with the development of cardiovascular disease (CVD) and type 2 diabetes. FACTORS CONTRIBUTING TO THE DEVELOPMENT OF METABOLIC SYNDROME ▪ Hypertension ▪ Hyperglycemia ▪ Hyperinsulinemia ▪ Dyslipidemia (low HDL, high oxLDL, and hypertriglyceridemia). ▪ Abdominal obesity. Excess accumulation of visceral abdominal or intramuscular adipose tissue, even in normal weight individual METABOLIC SYNDROME ASSOCIATED CONDITIONS ▪ Endothelial dysfunction/injury ▪ Atherogenic dyslipidemia (Elevated triglycerides, small LDL particles, low HDL) ▪ Insulin resistance ▪ Chronic low-grade inflammation CARDIOVASCULAR DISEASE (CVD) ▪ CVD is described as disease of the heart or blood vessels. ▪ Blood flow to the heart, brain or body can be reduced as the result of a blood clot (thrombosis), or by a build-up of fatty deposits inside an artery that cause the artery to harden and narrow (atherosclerosis). Type of CVD: ▪ coronary heart disease ▪ stroke ▪ peripheral arterial disease - narrowed arteries reduce blood flow to the limbs ▪ aortic disease etc. CARDIOVASCULAR RISK FACTORS  3) Smooth Muscle Cell 4) Plaque Formation: As 5) Plaque Rupture or Erosion: Activation: In response to smooth muscle cells proliferate Atherosclerotic plaques can endothelial injury, smooth muscle and accumulate in the intima, become unstable due to factors cells in the arterial wall become along with lipids, inflammatory like inflammation, mechanical activated. They proliferate and cells, and extracellular matrix stress, or erosion of the endothelial migrate from the media to the components, they form a fibrous surface. Plaque rupture or erosion intima, where they contribute to plaque. exposes the plaque's the formation of atherosclerotic prothrombotic core to the plaques. bloodstream 2) Macrophage Activation and Uptake: Macrophages residing in the arterial wall become activated in response to various stimuli, including the presence of modified LDL and inflammatory mediators. Once bound to scavenger receptors, modified LDL particles are internalized by macrophages through receptor-mediated endocytosis. As macrophages continue to take up modified LDL and accumulate cholesterol esters, they transform into foam cells. 1) LDL Accumulation: In the initial stages of atherosclerosis, LDL particles undergo oxidation 6) Thrombosis: Exposure of the plaque's contents, and enzymatic modifications, and including tissue factor, collagen, and other accumulate in the intima. These procoagulant molecules, triggers the coagulation modified LDL particles are cascade. Platelets adhere to the exposed collagen recognized by scavenger and form a thrombus, which can partially or completely receptors on the surface of occlude the artery. macrophages. LDL Low-density lipoprotein (LDL) is a type of lipoprotein that transports cholesterol and triglycerides from the liver to cells throughout the body. However, LDL oxidation is a key event in the development of atherosclerosis, the underlying cause of most cardiovascular diseases. Mechanisms contribute to the oxidation of LDL includes: 1. Reactive Oxygen Species (ROS): ROS can react with LDL particles, initiating lipid peroxidation and oxidation of LDL lipids. 2. Inflammatory Processes: Inflammatory cells, such as macrophages and neutrophils, release ROS and reactive nitrogen species (RNS) during the inflammatory response and oxidize LDL directly or indirectly by promoting lipid peroxidation. 3. Enzymatic Processes: Enzymes such as lipoxygenases, myeloperoxidase, and cyclooxygenases can oxidize LDL. 4. Glycation: Advanced glycation end products (AGEs) can modify LDL particles, making them more susceptible to oxidation. Glycation of LDL can occur in conditions associated with hyperglycemia, such as diabetes mellitus. CRP C-reactive protein (CRP). ❑ is a protein that the liver makes when there is inflammation in the body ❑ also called a marker of inflammation ❑ can be measured by high-sensitivity C-reactive protein (hs-CRP) test  Plasma CRP concentrations of 3 mg/L or higher are believed to be an independent predictor of metabolic syndrome.  The prolonged chronic inflammation of metabolic syndrome sets the stage for a feedback loop of worsening insulin resistance, impaired glucose tolerance, and abnormal lipid levels.  OBESITY Obesity has a profound impact on immune function, influencing both innate and adaptive immunity: 1. Chronic Inflammation Mechanism: Adipose (fat) tissue in obese individuals releases pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). 2. Altered Immune Cell Function Macrophages: In obesity, macrophages in adipose tissue shift from an anti- inflammatory (M2) phenotype to a pro-inflammatory (M1) phenotype, contributing to systemic inflammation. T Cells: Obesity leads to an increase in pro-inflammatory T cells (e.g., Th1 and Th17) and a decrease in regulatory T cells (Tregs), which help maintain immune tolerance and prevent autoimmune responses. B Cells: Altered B cell function can result in increased production of antibodies, which may contribute to inflammation and autoimmune diseases. 3. Dysregulation of Immune Responses Impaired Innate Immunity: The function of innate immune cells, such as neutrophils and natural killer (NK) cells, is often impaired in obesity, reducing the body's initial defense against pathogens. Impaired Adaptive Immunity: The adaptive immune response, which involves the activation of T and B cells, can also be compromised, leading to a weaker response to infections and vaccinations. 4. Impaired Vaccine Response Mechanism: Obesity can affect the immune system's ability to generate an adequate response to vaccines. 5. Increased Susceptibility to Infections Respiratory Infections: Obesity is associated with a higher risk of respiratory infections, including influenza and COVID-19. The increased adipose tissue can affect lung function and the immune response in the respiratory tract. Skin Infections: Impaired skin barrier function in obese individuals can lead to a higher risk of bacterial and fungal infections. 6. Impaired Wound Healing Mechanism: Obesity can impair blood flow and oxygen delivery to tissues, essential for effective wound healing.  HYPERTENSION Hypertension (high blood pressure) can significantly affect immune function : 1. Chronic Inflammation Mechanism: Hypertension is often associated with chronic low-grade inflammation. High blood pressure can damage blood vessel walls, leading to the release of inflammatory cytokines and the recruitment of immune cells to the site of injury. 2. Endothelial Dysfunction Mechanism: Hypertension can cause damage to the endothelium (the inner lining of blood vessels). This damage can impair the function of the endothelium, which plays a critical role in regulating immune responses and maintaining vascular health. 3. Altered Immune Cell Function Mechanism: High blood pressure can alter the function of various immune cells, including T cells, B cells, and macrophages. For instance, hypertension can cause T cells to become more pro-inflammatory and less effective at regulating immune responses. 4. Oxidative Stress Mechanism: Hypertension is associated with increased oxidative stress, characterized by an excess of reactive oxygen species (ROS). These ROS can damage cells and tissues, including immune cells. 5. Impacts on Specific Immune Functions Innate Immunity: Hypertension can impair the innate immune response, which is the body's first line of defense against pathogens. This includes reduced function of natural killer (NK) cells and macrophages. Adaptive Immunity: Hypertension can also affect adaptive immunity, including altered T cell responses and decreased antibody production by B cells. This can weaken the body's ability to mount a specific and effective response to infections. 6. Impaired Wound Healing Mechanism: High blood pressure can impair circulation, leading to reduced oxygen and nutrient delivery to tissues, which are essential for effective wound healing.  DIABETES MELLITUS ▪ Diabetes mellitus, particularly when poorly controlled, can significantly impair immune function. 1. Chronic Inflammation Mechanism: Elevated blood sugar levels lead to the production of advanced glycation end- products (AGEs) and activation of various inflammatory pathways. 2. Impaired Innate Immunity Neutrophil Dysfunction: Diabetes can impair the function of neutrophils, including their ability to adhere, migrate to infection sites, and perform phagocytosis. Macrophage Dysfunction: Hyperglycemia can alter the function of macrophages, reducing their ability to recognize and destroy pathogens. Natural Killer (NK) Cells: The activity of NK cells, which are crucial for early responses to viral infections, is often reduced in individuals with diabetes. 3. Altered Adaptive Immunity T Cell Dysfunction: Elevated glucose levels can impair T cell activation, differentiation, proliferation, and function. This can result in a less effective response to infections and a decreased ability to remember and respond to previously encountered pathogens. B Cell Dysfunction: Diabetes can also affect B cells, reducing their ability to produce antibodies efficiently. This can impair the body’s ability to respond to and clear infections. 4. Increased Susceptibility to Infections Bacterial Infections: People with diabetes are at increased risk for bacterial infections, such as skin infections (e.g., cellulitis), urinary tract infections, and respiratory infections. Fungal Infections: There is a higher prevalence of fungal infections, including Candida infections, in individuals with diabetes. Tuberculosis: Diabetes increases the risk of reactivation of latent tuberculosis. 5. Impaired Wound Healing Mechanism: High blood sugar levels can impair blood flow, reduce oxygen delivery to tissues, and interfere with the function of immune cells at wound sites. 6. Vaccine Response Mechanism: Diabetes can reduce the immune system's ability to respond adequately to vaccines. 7. Autoimmune Responses Mechanism: Type 1 diabetes is itself an autoimmune condition, where the immune system attacks insulin-producing beta cells in the pancreas. 8. Microbiota Imbalance Mechanism: Diabetes can alter the composition of the gut microbiota, which plays a crucial role in regulating immune responses. RESTRICTING DIETARY CHOLESTEROL – DOES IT STILL RELEVANT? DIETARY FLAVONOIDS AND ANTI-INFLAMMATION