The recently discovered
protein,
leptin, which is secreted by fat cells in response to changes in
body weight or energy, has been implicated in regulation of feed intake, energy expenditure and the neuroendocrine axis in rodents and humans.
Leptin was first identified as the gene product found deficient in the obese ob/ob mouse. Administration of
leptin to ob/ob mice led to improved reproduction as well as reduced feed intake and
weight loss. The porcine
leptin receptor has been cloned and is a member of the class 1
cytokine family of receptors.
Leptin has been implicated in the regulation of immune function and the
anorexia associated with disease. The
leptin receptor is localized in the brain and pituitary of the pig. The
leptin response to acute
inflammation is uncoupled from
anorexia and is differentially regulated among swine genotypes. In vitro studies demonstrated that the
leptin gene is expressed by porcine preadipocytes and
leptin gene expression is highly dependent on
dexamethasone induced preadipocyte differentiation. Hormonally driven preadipocyte recruitment and subsequent fat cell size may regulate
leptin gene expression in the pig. Expression of CCAAT-enhancer binding proteinalpha (
C/EBPalpha) mediates
insulin dependent preadipocyte
leptin gene expression during
lipid accretion. In contrast,
insulin independent
leptin gene expression may be maintained by
C/EBPalpha auto-activation and phosphorylation/dephosphorylation. Adipogenic
hormones may increase adipose tissue
leptin gene expression in the fetus indirectly by inducing preadipocyte recruitment and subsequent differentiation. Central administration of
leptin to pigs suppressed feed intake and stimulated
growth hormone (GH) secretion. Serum
leptin concentrations increased with age and
estradiol-induced
leptin mRNA expression in fat was age and weight dependent in prepuberal gilts. This occurred at the time of expected puberty in intact contemporaries and was associated with greater LH secretion. Further work demonstrated that
leptin acts directly on pituitary cells to enhance LH and GH secretion, and brain tissue to stimulate
gonadotropin releasing hormone secretion. Thus, development of nutritional schemes and (or) gene therapy to manipulate
leptin secretion will lead to practical methods of controlling appetite, growth and reproduction in farm animals, thereby increasing efficiency of lean meat production.