Pleiotrophin deficiency protects against high-fat diet-induced neuroinflammation: Implications for brain mitochondrial dysfunction and aberrant protein aggregation

Food Chem Toxicol. 2023 Feb:172:113578. doi: 10.1016/j.fct.2022.113578. Epub 2022 Dec 23.


Metabolic Syndrome (MetS) is a risk factor for the development of neurodegenerative diseases. Neuroinflammation associated with MetS may contribute significantly to neurodegeneration. Pleiotrophin (PTN) is a neurotrophic factor that modulates neuroinflammation and is a key player in regulating energy metabolism and thermogenesis, suggesting that PTN could be important in the connection between MetS and neuroinflammation. We have now used a high-fat diet (HFD)-induced obesity model in Ptn-/- mice. HFD and Ptn deletion caused alterations in circulating hormones including GIP, leptin and resistin. HFD produced in Ptn+/+ mice a neuroinflammatory state as observed in cerebral quantifications of proinflammatory markers, including Il1β, Tnfα and Ccl2. The upregulation of neuroinflammatory markers was prevented in Ptn-/- mice. Changes induced by HFD in genes related to mitochondrial biogenesis and dynamics were less pronounced in the brain of Ptn-/- mice and were accompanied by significant increases in the protein expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I and IV. HFD-induced changes in genes related to the elimination of protein aggregates were also less pronounced in the brain of Ptn-/- mice. This study provides substantial evidence that Ptn deletion protects against HFD-induced neuroinflammation, mitochondrial dysfunction, and aberrant protein aggregation, prominent features in neurodegenerative diseases.

Keywords: Metabolic syndrome; Neuroinflammation; Pleiotrophin; Ptprz1.

MeSH terms

  • Animals
  • Brain / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects
  • Mice
  • Neurodegenerative Diseases*
  • Neuroinflammatory Diseases
  • Protein Aggregates*


  • pleiotrophin
  • Protein Aggregates
  • Cytokines