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Fatty Acid Metabolism in Patients with PPARĪ³ Mutations
- Source :
- The Journal of Clinical Endocrinology & Metabolism. 93:4462-4470
- Publication Year :
- 2008
- Publisher :
- The Endocrine Society, 2008.
-
Abstract
- CONTEXT: PPARG mutations may cause insulin resistance and dyslipidemia, but little is known about the mechanisms of the abnormalities of lipid metabolism. OBJECTIVE: We hypothesized that in PPARG mutations, abnormal adipose tissue triglyceride storage causes insulin resistance. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: Whole-body and adipose tissue-specific metabolic phenotyping through arteriovenous blood sampling was made before and after a mixed meal including 13C-palmitic acid. Studies were performed in a 32-yr-old male with partial lipodystrophy and type 2 diabetes, heterozygous for the PPARG P467L mutation and in an apparently phenotypically normal 32-yr-old male heterozygous for the PPARG n.AAA553T mutation. Comparator groups were age- and sex-matched healthy participants (n=10) and type 2 diabetes sex-matched participants (n=6). RESULTS: The P467L patient had elevated unmodulated fasting and postprandial plasma nonesterified fatty acid (NEFA) concentrations, despite a low adipose tissue NEFA output. Instead, NEFA appeared to originate directly from triglyceride-rich lipoproteins: 13C-palmitic acid accumulated rapidly in the NEFA fraction, as a sign of impaired fatty acid trapping in tissues. In contrast to the Pparg haploinsufficient mouse, the patient with n.AAA553T mutation did not exhibit paradoxically insulin sensitive and showed a mostly normal metabolic pattern. CONCLUSIONS: The lipodystrophic PPARG P467L phenotype include excessive and uncontrolled generation of NEFA directly from triglyceride-rich lipoproteins, explaining high systemic NEFA concentrations, whereas the human PPARG haploinsufficiency is metabolically almost normal.
- Subjects :
- Adult
Male
Peroxisome proliferator-activated receptor gamma
medicine.medical_specialty
Lipoproteins
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Clinical Biochemistry
Palmitic Acid
Adipose tissue
Type 2 diabetes
Fatty Acids, Nonesterified
Biology
Biochemistry
chemistry.chemical_compound
Endocrinology
Insulin resistance
Reference Values
Internal medicine
medicine
Humans
Hypoglycemic Agents
Pioglitazone
Fatty acid metabolism
Genetic Carrier Screening
Insulin
Fatty Acids
Biochemistry (medical)
medicine.disease
Lipodystrophy, Familial Partial
PPAR gamma
Adipose Tissue
Amino Acid Substitution
Diabetes Mellitus, Type 2
chemistry
Mutation
Thiazolidinediones
Insulin Resistance
Lipodystrophy
Blood sampling
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....c23d1626a39756d72bfe2637037357a8