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Updated: Jun 8, 2025

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Published on: October 23, 2018
Low Phosphorus Causes Hepatic Energy Metabolism Disorder Through Dynamin-Related Protein 1-Mediated Mitochondrial
Jibin Lin1, Xueshan Li1, Kangle Lu1
1State Key Laboratory for Mariculture Breeding, Fisheries College of Jimei University, Xiamen, PR China; Xiamen Key Laboratory for Feed Quality Testing and Safety Evaluation, Fisheries College, Jimei University, Xiamen, PR China.
Background:
Low phosphorus (LP) diets perturb hepatic energy metabolism homeostasis in fish. However, the specific mechanisms in LP-induced hepatic energy metabolism disorders remain to be fully elucidated.
Objectives:
This study sought to elucidate the underlying mechanisms of mitochondria involved in LP-induced energy metabolism disorders.
Methods:
Spotted seabass were fed diets with 0.72% (S-AP, control) or 0.36% (S-LP) available phosphorus for 10 wk. Drp1 was knocked down or protein kinase (PK) A was activated using 8Br-cAMP (5 μM, a PKA activator) in spotted seabass hepatocytes under LP medium. Zebrafish were fed Z-LP diets (0.30% available phosphorus) containing Mdivi-1 (5 mg/kg, a Drp1 inhibitor) or 8Br-cAMP (0.5 mg/kg) for 6 wk. Biochemical and molecular parameters, along with transmission electron microscopy and immunofluorescence, were used to assess hepatic glycolipid metabolism, mitochondrial function, and morphology.
Results:
Spotted seabass fed S-LP diets showed reduced ATP (52%) and cAMP (52%) concentrations, along with reduced Drp1 (s582) (38%) and PKA (61%) phosphorylation concentrations in the liver compared with those fed S-AP diets (P < 0.05). Drp1 knockdown elevated ATP concentrations (1.99-fold), decreased mitochondrial DRP1 protein amounts (45%), and increased mitochondrial aspect ratio (1.82-fold) in LP-treated hepatocytes (P < 0.05). Furthermore, 8Br-cAMP-treated hepatocytes exhibited higher PKA phosphorylation (2.85-fold), ATP concentrations (1.60-fold), and mitochondrial aspect ratio (2.00-fold), along with decreased mitochondrial DRP1 protein concentrations (29%) under LP medium (P < 0.05). However, mutating s582 to alanine mimic Drp1 dephosphorylation decreased ATP concentrations (63%) and mitochondrial aspect ratio (53%) in 8Br-cAMP-treated hepatocytes (P < 0.05). In addition, zebrafish fed Z-LP diets containing Mdivi-1 or 8Br-cAMP had higher ATP concentrations (3.44-fold or 1.98-fold) than those fed Z-LP diets (P < 0.05).
Conclusions:
These findings provide a potential mechanistic elucidation for LP-induced energy metabolism disorders through the cAMP/PKA/Drp1-mediated mitochondrial fission signaling pathway.
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