A 15-year-old boy is brought to the emergency department by his father 10 minutes after falling into a frozen lake during ice fishing. He was in the water for less than 1 minute before his father managed to pull him out. On arrival, his clothes are still wet and he appears scared. His body temperature is 36.2°C (97.1°F), pulse is 102/min, blood pressure is 133/88 mm Hg. Which of the following mechanisms contributes most to maintaining this patient's core body temperature?

Involuntary muscular contractions

Increase in hypothalamic set point

Contraction of arrector pili muscles

A 24-year-old man presents for an annual check-up. He is a bodybuilder and tells you he is on a protein-rich diet that only allows for minimal carbohydrate intake. His friend suggests he try exogenous glucagon to help him lose some excess weight before an upcoming competition. Which of the following effects of glucagon is he attempting to exploit?

Increased lipolysis in adipose tissues

Increased glucose utilization by tissues

Decreased blood cholesterol level

Increased hepatic gluconeogenesis

Increased hepatic glycogenolysis

A 10-month-old boy with a seizure disorder is brought to the physician by his mother because of a 2-day history of vomiting and lethargy. Laboratory studies show a decreased serum glucose concentration with low ketones. Further testing confirms a deficiency in an enzyme involved in fatty acid oxidation. Which of the following enzymes is most likely deficient in this patient?

Glycerol-3-phosphate dehydrogenase

A 42-year-old woman comes to the physician for a routine health maintenance examination. She has generalized fatigue and has had difficulties doing her household duties for the past 3 months. She has eczema and gastroesophageal reflux disease. She has a history of using intravenous methamphetamine in her youth but has not used illicit drugs in 23 years. Her medications include topical clobetasol and pantoprazole. She is 160 cm (5 ft 3 in) tall and weighs 105 kg (231 lb); BMI is 42 kg/m2. Her temperature is 37°C (98.6°F), pulse is 95/min, and blood pressure is 145/90 mm Hg. The lungs are clear to auscultation. Cardiac examination shows no abnormalities. Pelvic examination shows a normal vagina and cervix. Laboratory studies show: Hemoglobin 13.1 g/dL Leukocyte count 7,800/mm3 Platelet count 312,000/mm3 Serum Na+ 141 mEq/L K+ 4.6 mEq/L Cl- 98 mEq/L Urea nitrogen 12 mg/dL Fasting glucose 110 mg/dL Creatinine 0.8 mg/dL Total cholesterol 269 mg/dL HDL-cholesterol 55 mg/dL LDL-cholesterol 160 mg/dL Triglycerides 320 mg/dL Urinalysis is within normal limits. An x-ray of the chest shows no abnormalities. She has not lost any weight over the past year despite following supervised weight loss programs, including various diets and exercise regimens. Which of the following is the most appropriate next step in management of this patient?

Phentermine and topiramate therapy and follow-up in 3 months

Metformin and statin therapy and follow-up in 3 months

You have been asked to deliver a lecture to medical students about the effects of various body hormones and neurotransmitters on the metabolism of glucose. Which of the following statements best describes the effects of sympathetic stimulation on glucose metabolism?

Epinephrine increases liver glycogenolysis.

Norepinephrine causes increased glucose absorption within the intestines.

Without epinephrine, insulin cannot act on the liver.

Peripheral tissues require epinephrine to take up glucose.

Sympathetic stimulation to alpha receptors of the pancreas increases insulin release.

A 35-year-old man comes to the physician because of fatigue and generalized weakness for the past year. He has noticed he has been having fewer bowel movements. He has had pain with defecation and small amounts of blood when wiping. He has not lost weight despite increased efforts to diet and exercise. He has had no fever, throat pain, or difficulty swallowing. His temperature is 36.5°C (97.7°F), pulse is 50/min, blood pressure is 120/90 mm Hg, and BMI is 35 kg/m2. Physical examination shows dry skin and a distended abdomen. There is 1+ pitting edema in the lower extremities. On neurological examination, deep tendon reflexes are 1+. Further evaluation of this patient is most likely to show which of the following findings?

Elevated serum low-density lipoprotein

Decreased plasma homocysteine concentrations

Decreased serum creatine kinase

Adipose tissue metabolism for USMLE Step 1: High-Yield Biochemistry Lessons

Adipose Tissue - The Body's Energy Bank

Histology of brown adipose tissue

White Adipose Tissue (WAT): Primary site for triglyceride storage. Functions in insulation and cushioning.
Brown Adipose Tissue (BAT): Specialized for non-shivering thermogenesis, crucial in newborns.

Feature	White Adipose Tissue (WAT)	Brown Adipose Tissue (BAT)
Primary Function	Energy Storage (Triglycerides)	Thermogenesis (Heat Production)
Mitochondria	Few	Abundant, high UCP-1 (Thermogenin)
Appearance	Large, single lipid droplet	Multiple small lipid droplets, brown color
Vascularity	Lower	Higher

Lipogenesis - Stocking the Pantry

Goal: Convert dietary fats & glucose into stored triglycerides (TGs) in adipocytes, primarily in the fed state.
Key Regulator: Insulin.
- Promotes glucose uptake via GLUT4 transporters.
- Activates Lipoprotein Lipase (LPL) on capillary endothelium.

Triglyceride Synthesis:
- Backbone: Glucose provides the $Glycerol-3-P$ backbone.
- Fatty Acids: LPL hydrolyzes TGs from chylomicrons/VLDL, releasing FFAs for uptake.
- Esterification: 3 FFAs + $Glycerol-3-P$ → Triglyceride.
📌 Mnemonic: 'LPL lets lipids pass' into the cell.

⭐ High-Yield: Insulin has a dual role: it stimulates LPL for fat storage while simultaneously inhibiting Hormone-Sensitive Lipase (HSL) to prevent fat breakdown. This ensures maximal energy storage when nutrients are abundant.

Lipolysis - Cashing in the Energy

Process: Breakdown of stored triglycerides (TGs) in adipocytes into free fatty acids (FFAs) and glycerol, releasing energy during fasting, exercise, or stress.
Key Enzyme: Hormone-Sensitive Lipase (HSL) is the rate-limiting enzyme.
- Activated by phosphorylation.
- Inhibited by dephosphorylation (driven by insulin).

Hormonal Control:

Activators (↓Insulin/↑Glucagon): Epinephrine, Glucagon, Cortisol.
Inhibitor (↑Insulin): Insulin promotes TG storage by inactivating HSL.

📌 Mnemonic: 'HSL is Hormone-Sensitive and Liberates' fatty acids.

Hormonal regulation of adipose tissue lipolysis

⭐ Exam Favorite: Adipocytes lack glycerol kinase. Therefore, the glycerol released during lipolysis cannot be re-used for TG synthesis within the adipocyte. It is transported to the liver for gluconeogenesis or glycolysis.

Adipokines - The Fat-Talk Hormones

Adipose tissue functions as an endocrine organ by secreting adipokines, which are hormones that regulate metabolism and inflammation.

Leptin: The satiety hormone. Secreted in proportion to fat mass, it acts on the hypothalamus to ↓ appetite. In obesity, leptin levels are ↑, but leptin resistance occurs.
Adiponectin: The insulin-sensitizing hormone. It ↑ glucose uptake and fatty acid oxidation. Secretion is ↓ in obesity.
Resistin: Induces insulin resistance. Its levels are ↑ in obesity.

⭐ Leptin deficiency is a rare cause of severe, early-onset obesity that is treatable with leptin replacement therapy.

High‑Yield Points - ⚡ Biggest Takeaways

In the fed state, insulin activates lipoprotein lipase (LPL) for triglyceride storage and inhibits hormone-sensitive lipase (HSL) to prevent fat breakdown.

In the fasting state, epinephrine and glucagon activate HSL, releasing free fatty acids (FFAs) and glycerol.

Hormone-sensitive lipase is the key, hormonally-regulated enzyme for lipolysis.

Adipocytes lack glycerol kinase, so glycerol must be transported to the liver.

GLUT4 is the primary, insulin-responsive glucose transporter on adipocytes.

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