Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease.
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.
To derive a systems view of how genetic loci interact in the context of tissue-specific molecular networks, we constructed an F2 intercross comprised of >500 mice from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mouse strains made genetically obese by the Leptin(ob/ob) mutation (Lep(ob)).
Our results demonstrate that chronic MC4R activation, even in NPY-deficient mice, does not mimic chronic antidiabetic, cardiovascular, or metabolic actions of leptin, and that NPY is not essential for hyperphagia or cardiovascular changes associated with diabetes.
The leptin-resistant db/ db mouse has been extensively studied as a model of diabetes-associated cardiomyopathy; however, data on the functional and morphological alterations in db/ db hearts are conflicting.
SD rats administered leptin immunogen also showed glucose intolerance, β- cell reduction in the pancreas, and deregulation of JAK2-STAT3/PI3K signaling, indicating that Lep rats were at risk of diabetes.
To gain further insight into the role of leptin in atherogenesis associated with diabetes, we investigated in the present study the role of this hormone in the regulation of macrophage lipoprotein lipase (LPL), a proatherogenic cytokine overexpressed in patients with type 2 diabetes.
Currently, PTP1B is being investigated by a number of companies as a promising target for leptin/insulin mimetics and in the treatment of diabetes and obesity.
Mathematical model of diabetes and lipid metabolism linked to diet, leptin sensitivity, insulin sensitivity and VLDLTG clearance predicts paths to health and type II diabetes.
These results suggest significant associations between BCAA concentrations and those for adiponectin, leptin and HOMA2-IR in individuals without diabetes.
Fasting glucose, plasma lipids, leptin, HbA(1c), and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes.
While leptin may be more effective than Gcgr siRNA at normalizing both glucose and lipid metabolism in STZ diabetes, Gcgr siRNA is more effective at reducing blood glucose levels in HFD/STZ diabetes.
Selective deletion of LEPR in these neurons with the Cre-loxP system, however, has previously failed to recapitulate, or only marginally recapitulated, the obesity and diabetes that are seen in LEPR-deficient Lepr <sup>db/db</sup> mice, suggesting that AGRP or POMC neurons are not directly required for the effects of leptin in vivo<sup>8-10</sup>.
Myriad biological effects of leptin may lead to broad therapeutic applications for various metabolic diseases, including diabetes and its complications; however, in contrast to its anorexic effect, the molecular mechanisms underlying adipopenic and glucose-lowering effects of leptin have not been fully understood.
As a step towards functional studies, we have characterized leptin receptors in human placenta from normal pregnancies and pregnancies associated with diabetes and pre-eclampsia.
To verify whether a diabetes family history might be a risk factor for the development, in adult age, of metabolic disorders, leptin, anthropometric and endocrine parameters were analysed in 95 babies with grandparents affected by type 2 diabetes (DF) and in 95 matched babies without diabetes family history (NDF).
These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits.