The db/db mice, with loss of function of the leptin receptor gene, suffer obesity, diabetes, and diabetic nephropathy.
However, we have ruled out any role for inflammatory-cell-intrinsic function of the leptin receptor in macrophage recruitment and/or retention dynamics, or polarization.
Cereal lectins could thus cause leptin resistance either indirectly, through effects on metabolism central to the proper functions of the leptin system, and/or directly, through binding to human leptin or leptin receptor, thereby affecting the function.
Hence, lectins have sufficient properties to affect the leptin system indirectly, through effects on metabolism central to the proper function of the leptin system, and possibly also directly through interaction with leptin or the leptin receptor.
The intriguing possibility of direct interaction between lectin and the leptin receptor could alter the function of the leptin receptor and translate into diseases of affluence [ 48, 61- 65, 65, 77- 82, 84- 91].
Interestingly, in human babies there is a sex difference in favour of higher leptin concentrations in female newborns [ 26], which is consistent with our above hypothesis about the function of the leptin surge in set point calibration.
We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function.
A variety of homozygous and compound heterozygous loss-of-function mutations in the leptin receptor have also been found in severely obese humans (Farooqi et al., 2007).
Leprdb/db mice are homozygous for a loss of function mutation in the Leptin receptor and become obese at ∼4 weeks of age.
The functions of leptin include the regulation of energy intake and consumption, modulation of the immune system, and induction of inflammatory and fibrogenic signals.
