Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs
Low-protein (LP) diets play a pivotal role in inducing skeletal muscle remodeling toward an oxidative phenotype in pigs, the underlying targets and mechanisms remain uncertain. This study aimed to investigate whether fibroblast growth factor 21 (FGF21), an endocrine signal associated with low protei...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-06-01
|
| Series: | Animal Nutrition |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405654525000204 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849415245326450688 |
|---|---|
| author | Shuo Li Pengbo Liang Bo Wang Jun Chen Jinming You Tiande Zou |
| author_facet | Shuo Li Pengbo Liang Bo Wang Jun Chen Jinming You Tiande Zou |
| author_sort | Shuo Li |
| collection | DOAJ |
| description | Low-protein (LP) diets play a pivotal role in inducing skeletal muscle remodeling toward an oxidative phenotype in pigs, the underlying targets and mechanisms remain uncertain. This study aimed to investigate whether fibroblast growth factor 21 (FGF21), an endocrine signal associated with low protein intake, mediates the effect of LP diets on myofiber type transition in pigs. Twenty-four healthy castrated weaned pigs (Landrace × Yorkshire) with an initial body weight (BW) of 7.25 ± 0.12 kg were assigned and fed one of two dietary treatments: a normal-protein (NP group) diet containing 19.78% crude protein (CP) or an LP diet containing 16.91% CP (LP group), over a 28-day trial. The LP diet was supplemented with crystalline amino acids to achieve an equal content of limiting amino acids. Additionally, half of the pigs in each dietary group were randomly administered an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (0.5 mg/kg BW, i.p.) weekly, while the remaining pigs received an equivalent dose of the vehicle (dimethyl sulfoxide). After blood sampling, all pigs were euthanized to collect liver and longissimus dorsi (LD) muscle samples. In vitro, we also explored the FGF21-induced myofiber conversion in porcine skeletal muscle satellite cells (PSCs), which were transfected with overexpression plasmid vector and ERK1/2 inhibitor. Results demonstrated that FGF21 was robustly increased by LP diets (P < 0.01), evidenced by elevated mRNA and protein expression levels of FGF21 in liver and LD muscle, as well as increased serum FGF21 concentration. Furthermore, pigs fed the LP diet exhibited a higher proportion of oxidative myofibers (P < 0.001), increased expression level of slow myosin heavy chain (MyHC) (P < 0.05) and myoglobin (P = 0.080), and enhanced succinate dehydrogenase activity (P < 0.01) in LD muscle. These effects were largely attenuated by ERK1/2 inhibitor administration. The activation of ERK1/2 and mTOR complex 1 (mTORC1) in the LD muscle of pigs fed LP diets was also suppressed by ERK1/2 inhibitor treatment (P < 0.05). In vitro, FGF21 overexpression increased slow MyHC protein expression, ERK1/2 phosphorylation and mTORC1 activity in PSCs (P < 0.05). Furthermore, inhibition of the ERK1/2 signaling significantly eliminated the FGF21-induced enhancement of oxidative myofiber expression and mTORC1 activity in PSCs (P < 0.05). Collectively, our findings suggest that the FGF21-ERK1/2 pathway serves as a key link mediator of LP diet-induced myofiber specification in pigs, and provide new insights into the understanding of the metabolic benefits of LP diets in pigs. |
| format | Article |
| id | doaj-art-fa8a655f6bbb49a08009a8d20df47cda |
| institution | Kabale University |
| issn | 2405-6545 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Animal Nutrition |
| spelling | doaj-art-fa8a655f6bbb49a08009a8d20df47cda2025-08-20T03:33:35ZengKeAi Communications Co., Ltd.Animal Nutrition2405-65452025-06-012120722110.1016/j.aninu.2025.03.001Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigsShuo Li0Pengbo Liang1Bo Wang2Jun Chen3Jinming You4Tiande Zou5Jiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, ChinaJiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, ChinaState Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100094, ChinaJiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, ChinaJiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, China; Corresponding authors.Jiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, China; Corresponding authors.Low-protein (LP) diets play a pivotal role in inducing skeletal muscle remodeling toward an oxidative phenotype in pigs, the underlying targets and mechanisms remain uncertain. This study aimed to investigate whether fibroblast growth factor 21 (FGF21), an endocrine signal associated with low protein intake, mediates the effect of LP diets on myofiber type transition in pigs. Twenty-four healthy castrated weaned pigs (Landrace × Yorkshire) with an initial body weight (BW) of 7.25 ± 0.12 kg were assigned and fed one of two dietary treatments: a normal-protein (NP group) diet containing 19.78% crude protein (CP) or an LP diet containing 16.91% CP (LP group), over a 28-day trial. The LP diet was supplemented with crystalline amino acids to achieve an equal content of limiting amino acids. Additionally, half of the pigs in each dietary group were randomly administered an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (0.5 mg/kg BW, i.p.) weekly, while the remaining pigs received an equivalent dose of the vehicle (dimethyl sulfoxide). After blood sampling, all pigs were euthanized to collect liver and longissimus dorsi (LD) muscle samples. In vitro, we also explored the FGF21-induced myofiber conversion in porcine skeletal muscle satellite cells (PSCs), which were transfected with overexpression plasmid vector and ERK1/2 inhibitor. Results demonstrated that FGF21 was robustly increased by LP diets (P < 0.01), evidenced by elevated mRNA and protein expression levels of FGF21 in liver and LD muscle, as well as increased serum FGF21 concentration. Furthermore, pigs fed the LP diet exhibited a higher proportion of oxidative myofibers (P < 0.001), increased expression level of slow myosin heavy chain (MyHC) (P < 0.05) and myoglobin (P = 0.080), and enhanced succinate dehydrogenase activity (P < 0.01) in LD muscle. These effects were largely attenuated by ERK1/2 inhibitor administration. The activation of ERK1/2 and mTOR complex 1 (mTORC1) in the LD muscle of pigs fed LP diets was also suppressed by ERK1/2 inhibitor treatment (P < 0.05). In vitro, FGF21 overexpression increased slow MyHC protein expression, ERK1/2 phosphorylation and mTORC1 activity in PSCs (P < 0.05). Furthermore, inhibition of the ERK1/2 signaling significantly eliminated the FGF21-induced enhancement of oxidative myofiber expression and mTORC1 activity in PSCs (P < 0.05). Collectively, our findings suggest that the FGF21-ERK1/2 pathway serves as a key link mediator of LP diet-induced myofiber specification in pigs, and provide new insights into the understanding of the metabolic benefits of LP diets in pigs.http://www.sciencedirect.com/science/article/pii/S2405654525000204Fibroblast growth factor 21Low-protein dietSkeletal muscleMyofiber typeExtracellular signal-regulated kinase 1/2 |
| spellingShingle | Shuo Li Pengbo Liang Bo Wang Jun Chen Jinming You Tiande Zou Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs Animal Nutrition Fibroblast growth factor 21 Low-protein diet Skeletal muscle Myofiber type Extracellular signal-regulated kinase 1/2 |
| title | Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs |
| title_full | Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs |
| title_fullStr | Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs |
| title_full_unstemmed | Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs |
| title_short | Fibroblast growth factor 21/extracellular signal-regulated kinase 1/2 pathway as a key link mediates the effects of low-protein diet on skeletal muscle fiber type transformation in pigs |
| title_sort | fibroblast growth factor 21 extracellular signal regulated kinase 1 2 pathway as a key link mediates the effects of low protein diet on skeletal muscle fiber type transformation in pigs |
| topic | Fibroblast growth factor 21 Low-protein diet Skeletal muscle Myofiber type Extracellular signal-regulated kinase 1/2 |
| url | http://www.sciencedirect.com/science/article/pii/S2405654525000204 |
| work_keys_str_mv | AT shuoli fibroblastgrowthfactor21extracellularsignalregulatedkinase12pathwayasakeylinkmediatestheeffectsoflowproteindietonskeletalmusclefibertypetransformationinpigs AT pengboliang fibroblastgrowthfactor21extracellularsignalregulatedkinase12pathwayasakeylinkmediatestheeffectsoflowproteindietonskeletalmusclefibertypetransformationinpigs AT bowang fibroblastgrowthfactor21extracellularsignalregulatedkinase12pathwayasakeylinkmediatestheeffectsoflowproteindietonskeletalmusclefibertypetransformationinpigs AT junchen fibroblastgrowthfactor21extracellularsignalregulatedkinase12pathwayasakeylinkmediatestheeffectsoflowproteindietonskeletalmusclefibertypetransformationinpigs AT jinmingyou fibroblastgrowthfactor21extracellularsignalregulatedkinase12pathwayasakeylinkmediatestheeffectsoflowproteindietonskeletalmusclefibertypetransformationinpigs AT tiandezou fibroblastgrowthfactor21extracellularsignalregulatedkinase12pathwayasakeylinkmediatestheeffectsoflowproteindietonskeletalmusclefibertypetransformationinpigs |