This mouse model has no white fat, resulting in abnormal levels of glucose, insulin, and leptin, making the A-ZIP/F-1 mice a good model for lipodystrophy and insulin resistance.
Lipodystrophy in rodents and humans is a severe model of insulin resistance, and we use a novel therapeutic approach with the administration of the newly discovered leptin to ameliorate many of these metabolic abnormalities.
A 36-year-old female with PL associated with a heterozygous PPARG mutation complicated by poorly controlled diabetes and severe, refractory hypertriglyceridaemia was enrolled in a National Institutes of Health (NIH) protocol to evaluate the role of r-metHuLeptin in lipodystrophy.
The aims of this study were to determine whether leptin replacement in lipodystrophy patients ameliorates their metabolic abnormalities over an extended period of time and whether leptin therapy is effective in the different forms of lipodystrophy.
These studies have been instrumental in advancing our understanding of the underlying molecular pathogenesis of ectopic lipid accumulation and insulin resistance, and have prompted the initiation and subsequent adoption of leptin replacement therapy in human lipodystrophies.
Leptin and total and high-molecular-weight adiponectin were measured in plasma of 16 BSCL1/AGPAT2 and 19 BSCL2/seipin patients and compared with heterozygous (n = 22) or nonmutated relatives (controls, n = 30); patients with Dunnigan-type partial lipodystrophy due to lamin A/C mutations (n = 23), HIV-related lipodystrophy (n = 124), and insulin receptor dysfunctions caused by mutations or autoantibodies (n = 17).
Leptin is not able to treat typical obesity; however, it is effective for reversing leptin deficiency-induced obesity and is possibly useful in lipodystrophy.
Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial.We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency.
Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin.
Increased expression of inflammatory genes and decreased leptin expression also occur in Cnot3<sup>ad-/-</sup> WAT, achieving levels similar to those in lipodystrophic aP2-nSrebp1c and Pparg<sup>ldi/+</sup> mice; thus, Cnot3<sup>ad-/-</sup> mice exhibit lipodystrophy.
Circulating levels of AFABP and EFABP are not decreased in LD despite adipose tissue loss in contrast to other adipokines including leptin and adiponectin.
Determine effects of metreleptin on diabetes, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), growth, and puberty in pediatric patients with lipodystrophy and low leptin.
We herein focus on the cross-regulation of fat and bone and propose that marrow fat accumulation and reduced serum leptin and adiponectin levels may play important roles in the pathophysiologic process of osteoporosis in patients with lipodystrophy.
The effect of recombinant leptin (metreleptin) therapy on facial soft tissue volume in patients with non-human immunodeficiency virus LD has not been quantified to date.