Key result
Reduced-protein diet in goats lowers renal GHR but increases IGF1 expression via JAK2 and STAT3.
Why the study?
To determine the effect of a low-protein diet on the expression of GHR and subsequent IGF1 signalling in the renal cortex of young male goats to verify whether organ-specific synthesis of IGF1 mRNA expression occurs.
A protein-reduced diet in young goats leads to tissue-specific increases in renal IGF1 mRNA expression, likely mediated by stimulated JAK2 and STAT3 expression despite reduced GHR expression.
Indicates GHR-independent JAK2/STAT3 activation of renal IGF1 under protein restriction in goats; hypothesis-generating, no clinical translation yet.
Feeding approaches for ruminants are changing to reduce N excretion as a major source of pollution. Based on the ruminohepatic cycle of N, it was assumed that the metabolism of ruminants could tolerate a reduced-protein diet well. However, metabolic changes such as a reduction in hepatic IGF1 mRNA expression, resulting in lower blood IGF1 levels due to decreased hepatic growth hormone receptor (GHR) expression, were found. Therefore, the aim of the present study was to determine the effect of a low-protein diet on the expression of GHR and subsequent IGF1 signalling in the renal cortex of young male goats to verify whether organ-specific synthesis of IGF1 mRNA expression occurs. Kidney cortex samples were obtained from eight goats fed a control diet (20% CP) and nine animals fed a reduced-protein diet (9% CP). The expression of GHR in the kidneys was reduced, whereas the expression of Janus kinase 2 (JAK2), suppressor of cytokine signalling 3 and signal transducers and activators of transcription 3 (STAT3) increased significantly. The stimulated JAK2 expression could modulate the expression of STAT3, which led to increased renal IGF1 mRNA expression. These results suggest that this increase in IGF1 mRNA expression in the kidneys is tissue-specific. This could be due to the autocrine/paracrine IGF1 effect on renal cell metabolism during a protein-reduced diet. These signalling pathways need further investigation to understand how and why low levels of protein stimulate IGF1 synthesis differently in the kidney than in the liver.
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Nevel et al. (2023) studied this question. Reduced-protein diet vs. Control diet (20% crude protein) was evaluated on Expression of GHR and subsequent IGF1 signalling in the renal cortex. A reduced-protein diet in young male goats reduced renal GHR expression but significantly increased JAK2 and STAT3 expression, leading to increased renal IGF1 mRNA expression.
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