Elsevier

Metabolism

Volume 64, Issue 1, January 2015, Pages 146-156
Metabolism

Leptin in the 21st Century
Leptin treatment: Facts and expectations

https://doi.org/10.1016/j.metabol.2014.07.014Get rights and content
Under a Creative Commons license
open access

Abstract

Leptin has key roles in the regulation of energy balance, body weight, metabolism, and endocrine function. Leptin levels are undetectable or very low in patients with lipodystrophy, hypothalamic amenorrhea, and congenital leptin deficiency (CLD) due to mutations in the leptin gene. For these patients, leptin replacement therapy with metreleptin (a recombinant leptin analog) has improved or normalized most of their phenotypes, including normalization of endocrine axes, decrease in insulin resistance, and improvement of lipid profile and hepatic steatosis. Remarkable weight loss has been observed in patients with CLD. Due to its effects, leptin therapy has also been evaluated in conditions where leptin levels are normal or high, such as common obesity, diabetes (types 1 and 2), and Rabson–Mendenhall syndrome. A better understanding of the physiological roles of leptin may lead to the development of leptin-based therapies for other prevalent disorders such as obesity-associated nonalcoholic fatty liver disease, depression and dementia.

Abbreviations

ALT
alanine transaminase
AST
aspartate transaminase
BMI
body mass index
CLD
congenital leptin deficiency
Cmax
peak serum concentration
CYP450
cytochrome P450
DXA
dual-energy X-ray absorptiometry
FGF21
fibroblast growth factor 21
FSH
follicle-stimulating hormone
GH
growth hormone
GnRH
gonadotropin-releasing hormone
HAART
highly active antiretroviral therapy
HbA1c
hemoglobin A1c
IGF-1
insulin-like factor-1
IGFBP
insulin-like growth factor-binding protein
LH
luteinizing hormone
LRT
leptin replacement therapy
NAFLD
nonalcoholic fatty liver disease
NASH
nonalcoholic steatohepatitis
Nf-κB
nuclear factor kappa-light-chain-enhancer of activated B cells
SOCS3
suppressor of cytokine signaling-3
POMC
proopiomelanocortin
PTP1B
protein tyrosine phosphatase 1B
Tmax
time to the maximum concentration
TNFα
tumor necrosis factor α
TSH
thyroid stimulating hormone

Keywords

Congenital leptin deficiency
Leptin
Metreleptin
Myalept
Obesity

Cited by (0)

1

Garran Rd, Building 131, Acton, ACT 0200, Australia.

2

South Australian Health and Medical Research Institute, PO Box 11060, Adelaide, SA 5001, Australia.