tetracycline and Lipodystrophy

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Arthritis; Diagnosis; Diarrhea; Humans; Lipodystrophy; Pathology; Tetracycline; Whipple Disease

Lipodystrophies are syndromes of adipose tissue degeneration associated with severe defects in lipid and glucose homeostasis. We report here the generation and analysis of Pparg(ldi), a targeted allele that confers conditional dominant lipodystrophy in mice. The Pparg(ldi) allele was generated by insertion of the Tet activator (tTA) and a tTA-regulated Flag-Pparg1 transgene into the Pparg gene. Unexpectedly, tTA elicits mild lipodystrophy, insulin resistance, and dyslipidemia, and the Flag-PPARgamma1 transgene surprisingly exacerbates these traits. Doxycycline can both completely prevent and reverse these phenotypes, providing a mouse model of inducible lipodystrophy. Embryonic fibroblasts from either Pparg(ldi/+) or the phenotypically similar aP2-nSrebp1c (Sr) transgenic mice undergo robust adipogenesis, suggesting that neither strain develops lipodystrophy because of defective adipocyte differentiation. In addition, Pparg(ldi/+) adipose tissue shares extensive gene expression aberrations with that of Sr mice, authenticating the phenotype at the molecular level and revealing a common expression signature of lipodystrophic fat. Thus, the Pparg(ldi/+) mouse provides a conditional animal model for studying lipodystrophy and its associated physiology and gene expression.

Topics: Adipogenesis; Alleles; Animals; Disease Models, Animal; Doxycycline; Fibroblasts; Gene Expression; Insulin Resistance; Lipodystrophy; Mice; Mice, Transgenic; PPAR gamma; Promoter Regions, Genetic; Sterol Regulatory Element Binding Protein 1; Tetracycline; Trans-Activators

Topics: Animals; Carbohydrate Metabolism; Hyperplasia; Hypertrophy; Insulin; Islets of Langerhans; Kidney Tubules; Lipid Metabolism; Lipodystrophy; Lipotropic Agents; Liver; Male; Rats; Tetracycline

Topics: Anti-Bacterial Agents; Bacteria; Drug Therapy; Electrons; Geriatrics; Humans; Intestines; Jejunum; Lipodystrophy; Microscopy; Microscopy, Electron; Pathology; Penicillins; Prednisolone; Prednisone; Tetracycline; Whipple Disease

Topics: Anti-Bacterial Agents; Bacteria; Biopsy; Candidiasis; Chloramphenicol; Clostridium; Corynebacterium; Electrons; Fusobacterium; Haemophilus; Humans; Jejunum; Lactobacillus; Leptospirosis; Lipodystrophy; Micrococcus; Microscopy; Microscopy, Electron; Neisseria; Penicillins; Staphylococcal Infections; Streptococcal Infections; Streptomyces; Sulfonamides; Tetracycline; Tooth Extraction; Veillonella; Whipple Disease

Topics: Anti-Bacterial Agents; Bacillus; Dermatologic Agents; Drug Therapy; Electrons; Humans; Intestines; Lipodystrophy; Microscopy; Microscopy, Electron; Neomycin; Pathology; Tetracycline; Whipple Disease

Topics: Adrenocorticotropic Hormone; Anti-Bacterial Agents; Humans; Intestines; Lipodystrophy; Methylprednisolone; Protein Synthesis Inhibitors; Tetracycline; Whipple Disease

Topics: Adrenocorticotropic Hormone; Anti-Bacterial Agents; Cortisone; Dexamethasone; Humans; Intestines; Lipodystrophy; Nystatin; Penicillins; Streptomycin; Tetracycline; Whipple Disease

Topics: Anti-Bacterial Agents; Biopsy; Chloramphenicol; Diarrhea; Follow-Up Studies; Humans; Lipodystrophy; Tetracycline; Whipple Disease