Korean J Pain.  2025 Apr;38(2):138-151. 10.3344/kjp.24388.

Octanoic acid-rich diet alleviates breast cancerinduced bone pain via the acyl-ghrelin/NPY pathway

• Xu L
• Hou L
• Cao C
• Li X

• KMID: 2566646
• DOI: http://doi.org/10.3344/kjp.24388

Abstract

Background
Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway.
Methods
First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway.
Results
An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated.
Conclusions
An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

Keyword

Breast Neoplasms; Cancer Pain; Caprylates; Diet; Ghrelin; Neuropeptide Y.

Figure

• 

  Fig. 1 Effects of different ratios of OA-rich diets on BW, daily food intake, nociceptive behaviors and inflammatory cytokines. Bone destruction is measured by X-ray (A). Hematoxylin-eosin staining (B) and the damaged area is located at the box. Percentage of change in BW (C). Daily food intake (D). PWT of modeling side (E) and contralateral side (F) are measured by von Frey filaments. PWL of modeling side (G) and contralateral side (H) are measured by a hot plate apparatus. Limb use score (I). The weight-bearing ratio (J) is measured via a dual-channel weight-averaging apparatus. Serum IL-1β (K), IL-6 (L) and TNF-α (M) as well as bone marrow IL-1β (N), IL-6 (O) and TNF-α (P) are measured by enzyme-linked immunosorbent assay. All the data are presented as the means ± SEMs. *P values < 0.05 versus the sham group. #P < 0.05 versus the CIBP group. CIBP: cancer-induced bone pain, OA: octanoic acid, BW: body weight, BL: baseline, PWT: paw withdrawal threshold, PWL: paw withdrawal latency, IL: interleukin, TNF: tumor necrosis factor.

• 

  Fig. 2 Effects of different ratios of OA-rich diets on the ghrelin-NPY pathway and the levels of total ghrelin and acyl-ghrelin in the serum and hypothalamus. The expression of ghrelin, CaMKKβ, p-AMPK/AMPK, p-mTOR/mTOR and NPY are measured by western blotting (A, B). β-Actin is used as a control, and the expression of all the proteins are normalized to those in the sham group. Serum total ghrelin (C) and acyl-ghrelin (D) are measured by enzyme-linked immunosorbent assay. The expression of hypothalamic ghrelin (E) and acyl-ghrelin (F) mRNAs are measured by real-time polymerase chain reaction. GAPDH is used as a control, and the expression of all mRNA are normalized to those in the sham group. All data are presented as the means ± SEMs. *P values < 0.05 versus the sham group. #P < 0.05 versus the CIBP group. CIBP: cancer-induced bone pain, OA: octanoic acid.

• 

  Fig. 3 Effects of the OA-rich diet on the levels of ghrelin in the serum and hypothalamus and the expression of GOAT with the administration of Go-Coa-Tat. The expression of ghrelin and GOAT are measured by western blotting (A, B). β-Actin is used as a control, and the expression of all the proteins are normalized to those in the sham group. Serum total ghrelin (C) and acyl-ghrelin (D) are measured by enzyme-linked immunosorbent assay. The expression of hypothalamic ghrelin (E) and acyl-ghrelin (F) mRNAs are measured by real-time polymerase chain reaction. GAPDH is used as a control, and the expression of all mRNA are normalized to those in the sham group. All data are presented as the means ± SEMs. *P values < 0.05 versus the sham group. #P < 0.05 versus the CIBP group. ^P < 0.05 versus the CIBP + OA group. CIBP: cancer-induced bone pain, OA: octanoic acid, GOAT: ghrelin O-acyl-transferase.

• 

  Fig. 4 Effects of OA-rich diets on the expression of the AMPK-mTOR pathway and NPY with the administration of Go-Coa-Tat. The expression of CaMKKβ, p-AMPK/AMPK, p-mTOR/mTOR and NPY are measured by western blotting (A). β-Actin is used as a control, and the expression of all the proteins are normalized to those in the sham group (B). All data are presented as the means ± SEMs. *P values < 0.05 versus the sham group. #P < 0.05 versus the CIBP group. ^P < 0.05 versus the CIBP + OA group. CIBP: cancer-induced bone pain, OA: octanoic acid.

• 

  Fig. 5 Effects of OA-rich diets on BW, daily food intake, nociceptive behaviors and inflammatory cytokines with the administration of Go-Coa-Tat. Percentage change in BW (A). Daily food intake (B). PWT of modeling side (C) and contralateral side (D) are measured by von Frey filaments. PWL of modeling side (E) and contralateral side (F) are measured by a hot plate apparatus. Limb use score (G). The weight-bearing ratio (H) is measured via a dual-channel weight-averaging apparatus. Serum IL-1β (I), IL-6 (J) and TNF-α (K) as well as bone marrow IL-1β (L), IL-6 (M) and TNF-α (N) are measured by enzyme-linked immunosorbent assay. All data are presented as the means ± SEMs. *P values < 0.05 versus the sham group. #P < 0.05 versus the CIBP group. ^P < 0.05 versus the CIBP + OA group. CIBP: cancer-induced bone pain, OA: octanoic acid, BW: body weight, BL: baseline, PWT: paw withdrawal threshold, PWL: paw withdrawal latency, IL: interleukin, TNF: tumor necrosis factor.

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