Leptin

Introduction
Leptin is a cytokine-like peptide secreted by adipocytes. It has a critical endocrine function, signalling to the hypothalamus the level of body fat reserves. Thus, in starvation, where fat reserves are very low, leptin is also low, and lack of leptin action in the brain stimulates hunger. This is most dramatically illustrated by the rare situation of genetic deficiency of leptin, where appetite becomes uncoupled from body fat stores, and so unremitting severe hyperphagia leads to severe early onset obesity, which is abolished by subcutaneous replacement of leptin Low leptin levels in starvation have other central effects in addition, including suppression of the hypothalamic-gonadal axis. Proof of this concept is the correction of weight loss-related amenorrhoea in female athletes by leptin therapy.

In congenital or acquired lipodystrophy, where fat tissue itself is absent or lost, reduced storage capacity for ingested fat leads to severe hypertriglyceridaemia, often complicated by pancreatitis, and severe insulin resistance. This problem is often exacerbated by low levels of leptin which produce hyperphagia and increase the ingested load of lipid. It has been clearly demonstrated in this situation that leptin replacement has dramatically beneficial effects on dyslipidaemia, insulin action and glycaemic control.

Clinical Indications
1. Diagnosis of Congenital Leptin Deficiency in Severe Early Onset Obesity
A rare cause of extreme early onset obesity is genetic deficiency of leptin. Thus the early evaluation of children who manifest hyperphagic obesity in the first few years of life should include serum leptin determination.

2. Diagnosis of leptin deficiency in congenital or acquired lipodystrophy
All generalised lipodystrophy and some cases of acquired lipodystrophy are associated with hypoleptinaemia. Correction of this with subcutaneous leptin therapy has dramatic metabolic benefits and so identification of candidates for leptin therapy in this group of patients is important.

3. Diagnosis of weight-related hypothalamic amenorrhoea
Demonstration of low or absent leptin may provide supportive biochemical evidence for extreme weight loss in the aetiology of secondary amenorrhoea.

Method Information
2 site timer resolved fluorescence immunoassay (DELFIA)

Patient Preparation
Fasting 9a.m. samples

Sample Requirements
0.5mls of serum, EDTA or Lithium heparain anticoagulated plasma

Sample Handling
Separate with 1 hour and freeze. Send frozen.

Interpretation
Appropriate Gender, Age and BMI related Reference range data will be provided

Quality Assessment
None available

Centres offering this assay
Cambridge Addenbrooke’s Hospital Endocrine Laboratory

References

Coll AP, Farooqi IS, O’Rahilly S. The hormonal control of food intake. Cell. 2007 Apr 20;129(2):251-62.

Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004 Sep 2;351(10):987-97.

Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, Cline GW, DePaoli AM, Taylor SI, Gorden P, Shulman GI. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest. 2002 May;109(10):1345-50.

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