<i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice
Type 2 diabetes mellitus (T2DM) is related with the incidence of sarcopenia and cognitive impairment that reduces quality of life in the elderly. Recent evidence has demonstrated that sarcopenia is associated with cognitive dysfunction, and muscle-derived endocrine factors might contribute to cognit...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/15/11/2559 |
| _version_ | 1797596913257676800 |
|---|---|
| author | Heaji Lee Sun Yeou Kim Yunsook Lim |
| author_facet | Heaji Lee Sun Yeou Kim Yunsook Lim |
| author_sort | Heaji Lee |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is related with the incidence of sarcopenia and cognitive impairment that reduces quality of life in the elderly. Recent evidence has demonstrated that sarcopenia is associated with cognitive dysfunction, and muscle-derived endocrine factors might contribute to cognitive function by the skeletal muscle–brain endocrine loop. This study investigated the beneficial effects of <i>Annona muricata</i> (AM, graviola) on multi-organ energy metabolism with muscle–brain connectivity via brain function-related myokines in mice. Body composition, fasting blood glucose level, insulin, HbA1c%, histopathological changes, and the protein levels of insulin-signaling, energy metabolism, neuroprotection, inflammation, and protein-degradation pathways were measured. AM extract (AME) treatment selectively enhanced insulin signaling in the skeletal muscle and hippocampus of T2DM mice. Furthermore, AME treatment effectively increased muscle-derived fibroblast growth factor 21 (FGF21), cathepsin-B (CTSB), irisin, brain-derived neurotrophic factor (BDNF), and liver-derived FGF21 that contribute to whole-body energy homeostasis. In particular, AME increased the levels of circulating myokines (FGF21, BDNF, irisin, and CTSB), and these were accordance with the hippocampal neurotrophic factors (BDNF and CTSB) in T2DM mice. In conclusion, we suggest that AME would be a potential nutraceutical for improving the energy metabolism associated with muscle–brain connectivity via brain function-related myokines in T2DM. |
| first_indexed | 2024-03-11T02:59:28Z |
| format | Article |
| id | doaj.art-48ed2348133a45998c6f01784a9a423d |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T02:59:28Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-48ed2348133a45998c6f01784a9a423d2023-11-18T08:21:45ZengMDPI AGNutrients2072-66432023-05-011511255910.3390/nu15112559<i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic MiceHeaji Lee0Sun Yeou Kim1Yunsook Lim2Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of KoreaGachon Institute of Pharmaceutical Science, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of KoreaDepartment of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of KoreaType 2 diabetes mellitus (T2DM) is related with the incidence of sarcopenia and cognitive impairment that reduces quality of life in the elderly. Recent evidence has demonstrated that sarcopenia is associated with cognitive dysfunction, and muscle-derived endocrine factors might contribute to cognitive function by the skeletal muscle–brain endocrine loop. This study investigated the beneficial effects of <i>Annona muricata</i> (AM, graviola) on multi-organ energy metabolism with muscle–brain connectivity via brain function-related myokines in mice. Body composition, fasting blood glucose level, insulin, HbA1c%, histopathological changes, and the protein levels of insulin-signaling, energy metabolism, neuroprotection, inflammation, and protein-degradation pathways were measured. AM extract (AME) treatment selectively enhanced insulin signaling in the skeletal muscle and hippocampus of T2DM mice. Furthermore, AME treatment effectively increased muscle-derived fibroblast growth factor 21 (FGF21), cathepsin-B (CTSB), irisin, brain-derived neurotrophic factor (BDNF), and liver-derived FGF21 that contribute to whole-body energy homeostasis. In particular, AME increased the levels of circulating myokines (FGF21, BDNF, irisin, and CTSB), and these were accordance with the hippocampal neurotrophic factors (BDNF and CTSB) in T2DM mice. In conclusion, we suggest that AME would be a potential nutraceutical for improving the energy metabolism associated with muscle–brain connectivity via brain function-related myokines in T2DM.https://www.mdpi.com/2072-6643/15/11/2559type 2 diabetes mellitusmyokineshepatokinesenergy metabolismskeletal musclebrain |
| spellingShingle | Heaji Lee Sun Yeou Kim Yunsook Lim <i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice Nutrients type 2 diabetes mellitus myokines hepatokines energy metabolism skeletal muscle brain |
| title | <i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice |
| title_full | <i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice |
| title_fullStr | <i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice |
| title_full_unstemmed | <i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice |
| title_short | <i>Annona muricate</i> Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice |
| title_sort | i annona muricate i extract supplementation contributes to improve aberrant multi organ energy metabolism via muscle brain connectivity in diabetic mice |
| topic | type 2 diabetes mellitus myokines hepatokines energy metabolism skeletal muscle brain |
| url | https://www.mdpi.com/2072-6643/15/11/2559 |
| work_keys_str_mv | AT heajilee iannonamuricateiextractsupplementationcontributestoimproveaberrantmultiorganenergymetabolismviamusclebrainconnectivityindiabeticmice AT sunyeoukim iannonamuricateiextractsupplementationcontributestoimproveaberrantmultiorganenergymetabolismviamusclebrainconnectivityindiabeticmice AT yunsooklim iannonamuricateiextractsupplementationcontributestoimproveaberrantmultiorganenergymetabolismviamusclebrainconnectivityindiabeticmice |