Ingestion of lean meat elevates muscle inositol hexakisphosphate kinase 1 protein content independent of a distinct post-prandial circulating proteome in young adults with obesity

Abstract

Background: We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. Aims: We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. Methods: Ten lean [Body mass index (BMI) (in kg/m 2): 22.7 ± 0.4; Homeostatic model assessment of insulin resistance (HOMA IR): 1.36 ± 0.17], 10 overweight (BMI: 27.1 ± 0.5; HOMA IR : 1.25 ± 0.11), and 10 obese (BMI: 35.9 ± 1.3; HOMA IR : 5.82 ± 0.81) adults received primed continuous L-[ring-13 C 6 ]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (R d). Results: Phenylalanine R d was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P N 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P b 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P N 0.05). Conclusions: These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.

Integrin‐associated ILK and PINCH1 protein content are reduced in skeletal muscle of maintenance haemodialysis patients

“…Total phenylalanine rate of appearance (R a ) is a measure of the appearance of dietary protein-derived phenylalanine and that from whole body protein breakdown into circulation (van Vliet et al 2018), whereas phenylalanine R d and MCR reflect whole-body amino acid clearance and its subsequent utilization and storage to the different tissue compartments within the body (Matthews, 2007;Barclay et al 2020).…”

“…2018), whereas phenylalanine R d and MCR reflect whole‐body amino acid clearance and its subsequent utilization and storage to the different tissue compartments within the body (Matthews, 2007; Barclay et al . 2020).…”

“…1999; Barclay et al . 2020). Raw data for insulin and phenylalanine metabolism are openly available via figshare: https://doi.org/10.6084/m9.figshare.12886943.…”

“…Whole body phenylalanine rate of disappearance (R d ), rate of appearance (R a ) and metabolic clearance rates (MCR values) were calculated as described previously (Bergman et al 1989;Gastaldelli et al 1999;Barclay et al 2020). Raw data for insulin and phenylalanine metabolism are openly available via figshare: https://doi.org/10.6084/m9.figshare.12886943.…”

“…Plasma insulin and endogenous glucose concentrations were used to model the measures of insulin sensitivity (ISI) (Matsuda index) (Matsuda & Defronzo, 1999): acute insulin response to glucose (AIR g ), second phase insulin response ( I 60-120 / G 60-120 ) (Lorenzo et al 2013) and disposition index (DI = S I × AIR g ) (Utzschneider et al 2009). Whole body phenylalanine rate of disappearance (R d ), rate of appearance (R a ) and metabolic clearance rates (MCR values) were calculated as described previously (Bergman et al 1989;Gastaldelli et al 1999;Barclay et al 2020). Raw data for insulin and phenylalanine metabolism are openly available via figshare: https://doi.org/10.6084/m9.figshare.12886943.…”