LIPID METABOLISM
AND
OBESITY
Aayush Nagar
PRESENTED Abhishek Bhadauria
BY: Abhishek Kumar Pate
Abhishek Kuri
Aditri Tiwari
Fatty Acid
Oxidation
Types of Fatty acid oxidation:
● β -oxidation
● α- Oxidation
● ω- Oxidation
● Oxidation of odd chain Fatty acid
Introduction to β-oxidation:-
• - Beta oxidation is the catabolic process by which fatty
acid molecules are broken down in the mitochondria
• - It involves successive removal of 2 carbon compound (acetyl coA)
• - Essential for energy production, especially during
fasting, prolonged exercise, or starvation.
• - Takes place in the mitochondrial matrix.
Overview of Beta
Oxidation:-
• - Location: Mitochondrial matrix(of liver, adipose tissue, muscle)
• - Substrate: Fatty Acyl-CoA
• - Products: Acetyl-CoA, FADH2, NADH
• - Final utilization: Acetyl-CoA enters the TCA
cycle; NADH and FADH2 go to ETC for ATP
production.
Steps of Beta Oxidation:-
• 1. Activation of Fatty
Acids – in cytoplasm by
Acyl-CoA synthetase
• 2. Transport into Mitochondria – via Carnitine
Shuttle (CPT-I, Translocase, CPT-II)
• 3. Beta Oxidation Proper:
Involves 4 steps:
1.Oxidation
2.Hydration
3.Oxidation
4.Cleavage
Energetics of Beta Oxidation:-
• -Palmitic acid (C16):
● -Stearic acid (C18):
Disorders Related to Beta Oxidation:-
• 1. SIDS: Sudden Infant Death Syndrome:
-10% cases of SIDS are due to deficiency of medium chain Acyl-CoA dehydrogenase
which causes defect in β oxidation
• 2. Jamaican Vomiting Sickness:
- Caused by hypoglycin A ( due to eating of unripe ackee fruit)
- Inhibits acyl-CoA dehydrogenase
● 3. Refsum disease:
- Neurological symptoms, retinitis pigmentosa and ataxia are seen
- There is defect in phytanic acid oxidase enzyme that leads to defect in α-
oxidation
- Accumulation of phytanic acid in brain causes the above mentioned
symptoms
● 4. Zellwager syndrome:(cerebrohepatorenal syndrome)
- Oxidation of very long chain Fatty acid is affected due to absence of
functional peroxisomes
Regulation of Beta Oxidation:-
Clinical Relevance:-
• - Important energy source in fasting, exercise
• - Deficiencies can be life-threatening in infants and during
metabolic stress
• - Diagnostic importance in metabolic medicine
Conclusion:-
• - Beta oxidation is vital for energy metabolism
• - Involves cyclic breakdown of fatty acids into acetyl-CoA
• - Regulated tightly by hormonal and intracellular factors
• - Understanding its mechanism is key for diagnosing
metabolic diseases
Cholesterol Synthesis and
Disorders
Overview
● • Cholesterol is a vital lipid molecule.
● • Synthesized mainly in the liver.
● • Precursor for hormones, bile acids, vitamin
D.
● • Disorders can lead to serious health issues.
Site and Location
● • Major site: Liver
● • Other sites: Intestine, adrenal cortex, gonads
● • Location in cells: Cytoplasm and smooth ER
Cholesterol Synthesis - Stepwise
● 1. Acetyl-CoA -> HMG-CoA
● 2. HMG-CoA -> Mevalonate (Rate-limiting step)
● 3. Mevalonate -> IPP
● 4. IPP -> FPP
● 5. FPP -> Squalene
● 6. Squalene -> Lanosterol
● 7. Lanosterol -> Cholesterol
Key Enzyme and Regulation
● • HMG-CoA reductase: Key enzyme
● • Upregulated by: Insulin, low cholesterol
● • Downregulated by: Glucagon, statins, high
cholesterol
Functions of Cholesterol
● • Precursor for:
● - Steroid hormones
● - Vitamin D
● - Bile acids
● • Maintains membrane structure and fluidity
Disorders - Hypercholesterolemia
● • Elevated LDL cholesterol
● • Risk of atherosclerosis
● • Causes: Genetic, diet, lifestyle, diseases like
hypothyroidism
Familial Hypercholesterolemia
● • Genetic disorder (Autosomal dominant)
● • Defect in LDL receptor
● • Symptoms: Xanthomas, early heart attacks
Treatment Options
● • Statins: Inhibit HMG-CoA reductase
● • Ezetimibe: Reduces absorption in intestine
● • PCSK9 inhibitors: Increase LDL clearance
● • Lifestyle: Diet, exercise
Summary
● • Cholesterol is essential but imbalance causes
disorders
● • Synthesized in liver from Acetyl-CoA
● • Disorders include hypercholesterolemia, genetic
syndromes
● • Management includes drugs and lifestyle changes
Obesity
Introduction to Obesity
● Obesity is a complex disease involving an excessive
amount of body fat.
● It is not just a cosmetic concern but a medical problem.
● Defined by Body Mass Index (BMI) ≥ 30 kg/m².
Etiology (Causes) of Obesity
● Genetic factors
● Environmental factors – sedentary lifestyle, high-calorie diet
● Psychological factors – stress eating, depression
● Endocrine disorders – hypothyroidism, Cushing’s syndrome
● Medications – steroids, antidepressants
Pathophysiology
● Positive energy balance: energy intake > energy expenditure
● Adipose tissue expands – hypertrophy and hyperplasia
● Dysregulation of hormones – leptin, insulin resistance
● Chronic low-grade inflammation
Complications of Obesity
● Cardiovascular diseases – hypertension, atherosclerosis
● Type 2 diabetes mellitus
● Respiratory problems – sleep apnea
● Musculoskeletal disorders – osteoarthritis
● Certain cancers – breast, colon, endometrial
Diagnosis and Classification
● BMI calculation: weight (kg)/height² (m²)
● BMI ≥ 30: Obese
● Waist circumference – central obesity
● Other tests: lipid profile, blood glucose
Management of Obesity
● Lifestyle changes – diet and physical activity
● Behavioral therapy – CBT, support groups
● Pharmacological treatment – orlistat, liraglutide
● Surgical options – bariatric surgery in severe cases
Prevention
● Healthy eating habits from early age
● Regular physical activity
● Avoid sedentary behavior (e.g., excessive screen time)
● Awareness programs in schools and colleges
Conclusion
● Obesity is a growing health challenge globally.
● Requires multidisciplinary approach for
effective management.
● Prevention and early intervention are key.