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

Richie Barclay; Joseph W. Beals; Jenny Drnevich; Brian S. Imai; Peter M. Yau; Alexander V. Ulanov; Neale A. Tillin; Martha  Villegas-Montes; Scott A. Paluska; Peter W. Watt; Michael  De Lisio; Nicholas A. Burd; Richard Mackenzie

doi:10.1016/j.metabol.2019.153996

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

Richie Barclay, Joseph W. Beals, Jenny Drnevich, Brian S. Imai, Peter M. Yau, Alexander V. Ulanov, Neale A. Tillin, Martha Villegas-Montes, Scott A. Paluska, Peter W. Watt, Michael De Lisio, Nicholas A. Burd, Richard Mackenzie

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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- ¹³C 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 > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 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.

Original language	English
Article number	153996
Number of pages	11
Journal	Metabolism: Clinical and Experimental
Volume	102
Early online date	31 Oct 2019
DOIs	https://doi.org/10.1016/j.metabol.2019.153996
Publication status	Published - Jan 2020
Externally published	Yes

Funding

We would like to thank University of Roehampton Sport and Exercise Science Research Centre (SESRC) technicians, Tom Reeve and Alison Carlisle, for their support with the project and organising safe transport of muscle and plasma samples. RDB, JWB, NAB, and RWM contributed to the conception and the design of the experiment. RDB, JWB, JD, BSI, PMY, AVU, MVM, SAP, NAV and RWM contributed to collection, analysis, and interpretation of data. RDB, JWB, NAT, PW, NT, NAB, and RWM contributed to drafting or revising intellectual content of the manuscript. RB, NAB, and RWM had primary responsibility for final content. All authors read and approved the final manuscript. This work was partly supported by the National Pork Board [grant numbers #14-205, 2016 and #16-012, 2016]. There are no conflicts of interests to disclose.

Funders	Funder number
National Pork Board	14-205, 16-012

Keywords

Insulin resistance
Obesity
Amino acids
Anabolic resistance
IP6K1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.metabol.2019.153996

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Barclay, R., Beals, J. W., Drnevich, J., Imai, B. S., Yau, P. M., Ulanov, A. V., Tillin, N. A., Villegas-Montes, M., Paluska, S. A., Watt, P. W., De Lisio, M., Burd, N. A., & Mackenzie, R. (2020). 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. Metabolism: Clinical and Experimental, 102, Article 153996. https://doi.org/10.1016/j.metabol.2019.153996

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. / Barclay, Richie; Beals, Joseph W.; Drnevich, Jenny et al.
In: Metabolism: Clinical and Experimental, Vol. 102, 153996, 01.2020.

Research output: Contribution to journal › Article › peer-review

Barclay, R, Beals, JW, Drnevich, J, Imai, BS, Yau, PM, Ulanov, AV, Tillin, NA, Villegas-Montes, M, Paluska, SA, Watt, PW, De Lisio, M, Burd, NA & Mackenzie, R 2020, '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', Metabolism: Clinical and Experimental, vol. 102, 153996. https://doi.org/10.1016/j.metabol.2019.153996

@article{646a0c91601d491182e2862a0a8dd6a0,

title = "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- 13C 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 > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 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.",

keywords = "Insulin resistance, Obesity, Amino acids, Anabolic resistance, IP6K1",

author = "Richie Barclay and Beals, \{Joseph W.\} and Jenny Drnevich and Imai, \{Brian S.\} and Yau, \{Peter M.\} and Ulanov, \{Alexander V.\} and Tillin, \{Neale A.\} and Martha Villegas-Montes and Paluska, \{Scott A.\} and Watt, \{Peter W.\} and \{De Lisio\}, Michael and Burd, \{Nicholas A.\} and Richard Mackenzie",

year = "2020",

month = jan,

doi = "10.1016/j.metabol.2019.153996",

language = "English",

volume = "102",

journal = "Metabolism: Clinical and Experimental",

issn = "0026-0495",

publisher = "W.B. Saunders",

}

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 A.

AU - Villegas-Montes, Martha

AU - Paluska, Scott A.

AU - Watt, Peter W.

AU - De Lisio, Michael

AU - Burd, Nicholas A.

AU - Mackenzie, Richard

PY - 2020/1

Y1 - 2020/1

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/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- 13C 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 > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 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.

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/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- 13C 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 > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 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.

KW - Insulin resistance

KW - Obesity

KW - Amino acids

KW - Anabolic resistance

KW - IP6K1

UR - https://www.scopus.com/pages/publications/85074647852

U2 - 10.1016/j.metabol.2019.153996

DO - 10.1016/j.metabol.2019.153996

M3 - Article

SN - 0026-0495

VL - 102

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

M1 - 153996

ER -

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

Funding

Keywords

UN SDGs

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