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

TY - JOUR

T1 - 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

AU - Barclay, Richie

AU - Beals, Joseph W.

AU - Drnevich, Jenny

AU - Imai, Brian S.

AU - Yau, Peter M.

AU - Ulanov, Alexander V.

AU - Tillin, Neale

AU - Paluska, Scott A.

AU - Watt, Peter W.

AU - De Lisio, Michael

AU - Burd, Nichlolas A.

AU - Mackenzie, Richard

AU - Villegas-Montes, Martha

N1 - obesity, amino acids, anabolic resistance, IP6K1.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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/m2): 22.7 ± 0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ± 0.17], 10 overweight (BMI: 27.1 ± 0.5; HOMAIR: 1.25 ± 0.11), and 10 obese (BMI: 35.9 ± 1.3; HOMAIR: 5.82 ± 0.81) adults received primed continuous L-[ring-13C6]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 (Rd). Results Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = .056; 120 & 300 min, P > .05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < .05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > .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.

AB - 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/m2): 22.7 ± 0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ± 0.17], 10 overweight (BMI: 27.1 ± 0.5; HOMAIR: 1.25 ± 0.11), and 10 obese (BMI: 35.9 ± 1.3; HOMAIR: 5.82 ± 0.81) adults received primed continuous L-[ring-13C6]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 (Rd). Results Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = .056; 120 & 300 min, P > .05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < .05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > .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.

KW - Insulin resistance

KW - Obesity

KW - Amino Acids

KW - anabolic resistance

KW - proteomics

KW - insulin signalling

KW - skeletal muscle

KW - IP6K1

U2 - 10.1016/j.metabol.2019.153996

DO - 10.1016/j.metabol.2019.153996

M3 - Article

VL - 102

JO - Metabolism Journal

JF - Metabolism Journal

M1 - 153996

ER -