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Jan 3, 2014

Age-Related Obesity Tied to Shutdown of Brown Fat Activity

  • Researchers in Japan report that they have discovered that the thermogenic activity of brown fat, which is located in the backs of our necks and helps burn white fat around midsections, is reduced with aging. The result is age-related obesity.

    The good news: The scientists also discovered a possible metabolic on/off switch that could reactivate brown fat.

    “Platelet-activating factor receptor (PAFR)-deficient mice developed a more severe obese state characterized by higher body mass (∼25%) and epididymal fat mass (∼55%) with age than that of wild-type (WT) littermates.” wrote the investigators in the FASEB journal. “A 38−81% reduction in β31-adrenergic receptor (AR) and uncoupling protein 1 (UCP1) mRNA and protein levels was observed in the interscapular brown adipose tissue (BAT) of PAFR-deficient mice…The stimulation of brown adipocytes by PAF induced the expression of β3-AR mRNA and protein (1.5- and 1.9-fold, respectively), but not that of UCP1. These results indicate that obesity in PAFR-deficient mice resulted from impaired BAT activity and suggest that the antiobese function of PAF occurs through β3-AR/UCP1 expression in BAT.”

    “Future studies on how PAF/PAFR signaling controls UCP1 levels through beta3-AR production in the BAT of animals and humans may reveal new therapeutic targets to treat metabolic disorders associated with obesity,” said Junko Sugatani, Ph.D., a researcher involved in the work from the department of pharmaco-biochemistry at the school of pharmaceutical sciences at the University of Shizuoka. Dr. Sugatani is one of the authors of the journal article entitled “Antiobese function of platelet-activating factor: increased adiposity in platelet-activating factor receptor-deficient mice with age.”

    Findings from the team’s PAFR-KO genetic model reveal that PAFR-deficiency causes brown adipose tissue (BAT) dysfunction, which converges to induce the development of obesity, due to impaired thermogenic activity of BAT. This study could elucidate the molecular mechanism underlying the PAF/PAF receptor-mediated anti-obesity, leading to the development of new targets for the treatment of obesity and related disorders such as diabetes, high blood pressure, heart disease, cancer, infertility, and ulcers.



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