Leptin (22-56), human

A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

A key pathology of Alzheimer's disease (AD) is amyloid β (Aβ) accumulation that triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However, as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.

Elevated leptin fragments in renal failure correlate with BMI and haematopoiesis and are normalized by haemodialysis

Objective: Leptin is an adipocyte hormone important in appetite, energy homeostasis, neuroendocrine and haematopoietic function. Patients with renal failure often have elevated total and free leptin levels. Biologically active leptin fragments (leptin(22-56) and leptin(57-92)) have been identified, but whether these fragments are affected by renal failure and/or haemodialysis (HD) is not known.
Research methods: Leptin, leptin(22-56) and leptin(57-92) levels were measured in 28 HD patients [14 men, 14 women, age 45.5 +/- 16.4 years, body mass index (BMI) 23.8 +/- 3.6 kg/m2] and 25 healthy controls with similar age and BMI. In 18 HD patients, leptin and fragment levels were measured before and after 2 consecutive dialysis treatments and on the intermediate, dialysis-free day.
Results: Baseline leptin levels were higher in HD patients vs. controls (69.3 +/- 62.2 ng/ml vs. 30.4 +/- 32.7, P < 0.02) as were leptin(22-56) (7.14 +/- 7.04 ng/ml vs. 1.86 +/- 1.84, P < 0.02) and leptin(57-92) (5.94 +/- 6.08 ng/ml vs. 1.58 +/- 1.98, P < 0.02). Baseline leptin and fragment levels correlated significantly and independently with BMI in HD patients (r = 0.70, r = 0.59, r = 0.72, respectively, P < 0.001). After each HD session, leptin levels were reduced to levels not different from controls, but increased on the intermediate, dialysis-free day. Similar to and independently from total leptin, both leptin fragments were reduced after the first HD session to levels not different from controls. The reduction in leptin levels was higher with synthetic vs. cellulosic membrane types (37.7 +/- 23.5%vs. 18.1 +/- 21.8%, P < 0.03). Leptin correlated weakly with the erythropoietin to haematocrit ratio (T = -0.20, P = 0.14), while leptin(22-56) had a significant negative correlation with this index (T = -0.42, P < 0.01), suggesting that this fragment may favour haematopoiesis.
Discussion: Leptin fragments are detected in human serum, and both leptin and leptin fragments correlate with BMI, are significantly elevated in HD patients compared to controls, and are significantly decreased by haemodialysis. The elevated leptin fragments may have important physiological significance for the anorexia, hypogonadism, and anaemia commonly seen in HD patients, but this remains to be conclusively shown by interventional trials.

Leptin and leptin receptor expression in the myometrium and uterine myomas: Is leptin involved in tumor development?

Leptin, the product of the obesity (ob) gene, along with its receptors (Ob-Rs), is expressed in several tissues and organs. Evidence has been provided that leptin, in addition to being involved in obesity development, plays a role in the regulation of the female reproductive system, angiogenesis and tumor growth. Uterine myoma is a rather common disease that develops more frequently in obese than lean women, where plasma leptin concentrations are elevated. RT-PCR and Western blotting showed that leptin was expressed, as mRNA and protein, in several uterine myomas but not in normal myometrium, while leptin receptors were expressed in both tissues. Immunocytochemistry indicated that leptin-immunoreactivity was located in both myometrial cells and blood-vessel walls of uterine myomas. Leptin(22-56), at concentrations of 10(-7) and 10(-6) M, enhanced the proliferative activity of both the normal myometrium and myoma cells in primary culture. Taken together, our findings allow us to suggest that leptin, acting through autocrine-paracrine mechanism(s), may be involved in the development of uterine myomas.