Primary (hereditary) lipodystrophies
Primary causes of lipodystrophies are driven by inherited or congenital genome alterations, most commonly in the form of point mutations.
- Familial lipodystrophies: associated with a mutation in the LMNA gene (autosomal dominant inheritance). Upon puberty, patients lose subcutaneous fat on the limbs, and later in the abdomen and chest. Cushingoid redistribution with fat accumulation on the face, neck, and intra-abdominally is possible.
- Congenital generalized lipodystrophy: an autosomal recessive disorder caused by a mutation in the AGPAT2 gene (chromosome 9q34). It manifests with an almost complete absence of adipose tissue and prominent muscle definition even in newborns. Triglyceride synthesis by adipocytes is impaired, leading to a deficiency of phospholipids required for cell membranes and signal transduction.
Secondary and acquired forms
Secondary lipodystrophies develop under the influence of external factors or comorbid conditions:
- HIV- and therapy-associated: occur in HIV-positive children receiving antiretroviral therapy (protease inhibitors). Localized fat loss occurs on the face and limbs, with potential excessive accumulation in the neck region due to preadipocyte apoptosis.
- Acquired partial lipodystrophy: characterized by the disappearance of fat on the face, neck, and upper trunk, with simultaneous excessive deposition on the buttocks and thighs. It is frequently associated with autoimmune diseases such as systemic lupus erythematosus.
- Generalized acquired form: affects extensive areas (face, limbs, palms, soles). In 25% of cases, it is associated with panniculitis (inflammation of the subcutaneous adipose tissue with destruction of adipocytes) or autoimmune processes (juvenile dermatomyositis).
Complications and treatment approaches
Deficiency and redistribution of adipose tissue lead to severe systemic disorders:
- Type 2 diabetes mellitus (against the background of relative hypoinsulinemia).
- Acute pancreatitis caused by hypertriglyceridemia.
- Hepatic steatosis and cirrhosis (steatosis develops in the majority of patients with the generalized acquired form, and cirrhosis in 20% of patients).
Therapeutic directions:
- Etiotropic therapy to eliminate the underlying cause.
- Surgical correction (plastic surgery for fat deficiency, liposuction for excessive neck deposits).
- Conservative methods (diet and weight loss to reduce fat accumulation in unaffected areas).
Briefly: answers to topical questions
Which classes of drugs cause secondary lipodystrophy in HIV infection?
Secondary lipodystrophy in HIV infection is caused by protease inhibitors. These drugs disrupt the differentiation of subcutaneous preadipocytes, leading to their apoptosis and localized loss of subcutaneous fat.
With which autoimmune diseases is acquired partial lipodystrophy associated?
Acquired partial lipodystrophy is associated with the following autoimmune diseases:
- Systemic lupus erythematosus
- Juvenile dermatomyositis
What is the pathogenesis of type 2 diabetes mellitus in lipodystrophies?
In congenital generalized lipodystrophy, type 2 diabetes mellitus is listed as a complication resulting from relative hypoinsulinemia. Overall, in lipodystrophies, impaired development, distribution, or survival of adipocytes leads to the inability of adipose tissue to adequately store lipids; excess lipids are deposited ectopically in the liver, muscles, and pancreas, causing severe insulin resistance.
Lipodystrophy is either genetic (LMNA/AGPAT2), HIV therapy-induced, or autoimmune panniculitis-related. The primary target organs for complications are the liver (steatosis/cirrhosis) and the pancreas (pancreatitis).
Class and exam questions
Which genetic mutations cause primary lipodystrophies?
Primary familial forms are associated with an LMNA gene mutation (autosomal dominant). The congenital generalized form is caused by a mutation in the AGPAT2 gene on chromosome 9.
Why does lipodystrophy develop in HIV infection?
The cause is antiretroviral drugs (protease inhibitors), which disrupt the normal differentiation of subcutaneous preadipocytes and induce their apoptosis.
What severe hepatic complications can occur in lipodystrophies?
Patients frequently develop hepatic steatosis due to prolonged fat accumulation in hepatocytes, and in some patients (e.g., with the generalized acquired form), it can progress to liver cirrhosis.
What inflammatory processes are associated with the generalized acquired form?
In 25% of cases, it is associated with panniculitis—a progressive inflammatory lesion of the subcutaneous adipose tissue leading to the destruction of adipocytes and their replacement by connective tissue.
What else to study on this topic
- Pathogenesis of impaired triglyceride synthesis and phospholipid deficiency in AGPAT2 mutations
- The role of protease inhibitors in preadipocyte apoptosis
- Visceral form of panniculitis and involvement of internal organ adipocytes
- Mechanisms of hypertriglyceridemia and acute pancreatitis
- The relationship between lipodystrophies, autoimmune diseases, and SLE
Master the entire topic in the "Pathophysiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Lipodystrophies" and another 4,913 pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 135 video lessons on the subject
Other topics in the section "Chapter 10. Disorders of Lipid Metabolism"
Free video lessons: pathophysiologyShort lessons with lecture notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.