By 6 weeks of age, TGPAT animals had almost completely gained proportionality, with only mild brain sparing, and WAT stores were accumulating to an appropriate mass for body weight.
Together with work on Alk (Cheng et al., 2011), our study reveals the existence of region specific mechanisms for brain sparing and suggests possible cellular and molecular routes by which early nutrient restriction may affect mammalian brain development and growth.
Later, fetal middle cerebral artery flow shows decreased resistance, indicating brain sparing, and eventually, abnormal venous Doppler results (ductus venosus waveforms and umbilical vein pulsatility) suggest fetal cardiac dysfunction.
The brain sparing effect and priority to brain over muscle becomes inevitable in these circumstances and we suggest that insulin resistance is a mechanism by which this shift in balance during development is maintained in adult life as well.
Taken together, these results suggest that the neural manifestations of the SAT are not widespread throughout the brain, sparing sensory, motor and some higher association areas.
Above the threshold, there was brain sparing (reduced body weight with an increase in brain/body weight ratio) and a targeting of the liver (reduced liver/body weight).
At P21, brown adipose tissue and liver weight normalized to body weight, and the brain sparing was less marked, but appreciable WAT stores had still failed to develop in the mutant animals and circulating leptin levels were low (WT 3.7 ± 0.4 ng mL−1, n = 13; TGPAT 1.0 ± 0.1 ng mL−1, n = 11; P < 0.001 by Students' t-test).
The brain sparing phenomenon in the fetus is a protective mechanism aimed at maintaining sufficient blood flow towards the brain during chronic or acute fetal stress, such as that caused by hypoxemia or utero-placental insufficiency.
Thus, a brain sparing role for Grb10 through the established interaction with mTOR [ 46, 47] is plausible.
In severely affected symptomatic FTD-3 cases, we have previously, with H2O PET rCBF measurements, found pronounced and widespread decreased CBF in most of the brain sparing the visual cortex, basal ganglia and cerebellum.
