Genotype - phenotype correlation in an adolescent girl with pathogenic PPARy genetic variation that caused severe hypertriglyceridemia and early onset type 2 diabetes

Abstract

Severe hypertriglyceridemia (HTG) (>885 mg/dl) can be caused by familial partial lipodystrophy Type 3 (FPLD 3), an autosomal dominant disorder caused by a loss of function of the peroxisome proliferator activated receptor gamma (PPARG), characterized by abnormal distribution of fat and metabolic derangements. 16 year old female (body mass index, BMI 23.5 kg/m 2 ) was hospitalized twice for pancreatitis (TG level >2200 mg/dl). She was managed with bowel rest, insulin infusion, and plasmapheresis. On a low fat 10 g daily diet and fenofibrate 160 mg daily her fasting TG had decreased to 411 mg/dL (range 0-149). Results: She had a normal leptin level.Panel testing of genes involved in triglyceride metabolism revealed a known pathogenic variant in PPARG gene (c.452A>G p.Tyr151Cys). A second variant detected in this gene, c.1003G>C (p.Val335Leu), is considered benign. HbA1C of 6.6% and two hours oral glucose tolerance test confirmed Type 2 diabetes (T2DM). We outline the earliest description of T2DM in an adolescent with a pathogenic variant of PPARG. PPARG related FLPD 3 should be considered in lean children presenting with severe HTG and insulin resistance and treatment with PPARy agonists Thiazolidinediones should be considered.

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

“…The main biological mechanism described for punicic acid involves the modulation of the differential expression of peroxisome proliferator-activated receptors (PPARs), which control the expression of genes involved in cell differentiation and proliferation, regulate enzymes involved in lipids metabolism, and glucose homeostasis. In addition, PPARs are closely related to the activation and production of pro-inflammatory biomarkers [16][17][18][19]. While the antioxidant and anti-inflammatory properties of punicic acid may provide beneficial effects on the treatment of NDs, the way it interacts in different pathways related to the progression of NDs may give it advantages over other anti-oxidative nutraceuticals.…”