Accumulating evidence suggests defective energy metabolism in ALS patients, which contributes to weight loss and a poor prognosis.
Lipid metabolism disorders have been widely reported in patients with ALS, presenting with hypercholesterolemia, hypertriglyceridemia, and other mixed dyslipidemias. Leptin, an adipokine, plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Nagel et al. suggested that leptin concentrations were positively correlated with the survival rate in ALS patients, indicating protective effects of leptin in patients with ALS.
Serum leptin concentration is strongly correlated with body weight or BMI, which was also confirmed in this study written by scientists from Chinese Academy of Medical Sciences. And higher body weight and BMI have been found to be associated with a lower risk of ALS and better prognosis in ALS patients.
Adipokines are a group of factors released or secreted by adipose tissue and have many physiological functions, such as fat distribution, energy expenditure, appetite and satiety regulation, insulin secretion and sensitivity, and inflammation.
Previous studies on the biological functions of adiponectin provide some evidence that adiponectin is beneficial in ALS. As one of the most abundant adipokines secreted by adipocytes, adiponectin functions in multiple physiological processes, including insulin sensitization, glucose regulation, lipid metabolism, and anti-inflammatory and antiapoptotic activities.
Fifty-two subjects were recruited between October 2020 and January 2022 among patients newly diagnosed with ALS in the Neurology Department of Peking Union Medical College Hospital. The study also included 24 healthy participants to compare adipokines and other metabolic biomarkers.
When comparing adipokines in patients and controls, the authors, found significant differences in the levels of adiponectin, adipsin, resistin, and visfatin between the two groups.
ALS patients had higher levels of adipokines (adiponectin, adipsin, resistin, and visfatin) and other metabolic biomarkers [C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide, and plasminogen activator inhibitor type 1] than controls.
Leptin levels in serum were positively correlated with body mass index, body fat, and visceral fat index.
Adiponectin was positively correlated with the visceral fat index and showed a positive correlation with the ALSFRS-R and a negative correlation with baseline disease progression.
Lower leptin and adiponectin levels were correlated with faster disease progression. After adjusting for confounders, lower adiponectin levels and higher visfatin levels were independently correlated with faster disease progression.
Berberine, an isoquinoline alkaloid, has been shown to increase adiponectin expression, which partly explains its beneficial effects on metabolic disturbances. Mice fed the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both omega-3 fatty acids, have also shown increased plasma adiponectin. Curcumin, capsaicin, gingerol, and catechins have also been found to increase adiponectin expression.