TY - JOUR
T1 - Picolinic acid, a tryptophan oxidation product, does not impact bone mineral density but increases marrow adiposity
AU - Ding, Kehong
AU - McGee-Lawrence, Meghan E.
AU - Kaiser, Helen
AU - Sharma, Anuj K.
AU - Pierce, Jessica L.
AU - Irsik, Debra L.
AU - Bollag, Wendy B.
AU - Xu, Jianrui
AU - Zhong, Qing
AU - Hill, William D
AU - Shi, Xing Ming
AU - Fulzele, Sadanand
AU - Kennedy, Eileen J.
AU - Elsalanty, Mohammed Elsayed
AU - Hamrick, Mark W.
AU - Isales, Carlos M.
PY - 2020/5
Y1 - 2020/5
N2 - Tryptophan is an essential amino acid catabolized initially to kynurenine (kyn), an immunomodulatory metabolite that we have previously shown to promote bone loss. Kyn levels increase with aging and have also been associated with neurodegenerative disorders. Picolinic acid (PA) is another tryptophan metabolite downstream of kyn. However, in contrast to kyn, PA is reported to be neuroprotective and further, to promote osteogenesis in vitro. Thus, we hypothesized that PA might be osteoprotective in vivo. In an IACUC-approved protocol, we fed PA to aged (23-month-old) C57BL/6 mice for eight weeks. In an effort to determine potential interactions of PA with dietary protein we also fed PA in a low-protein diet (8%). The mice were divided into four groups: Control (18% dietary protein), +PA (700 ppm); Low-protein (8%), +PA (700 ppm). The PA feedings had no impact on mouse weight, body composition or bone density. At sacrifice bone and stem cells were collected for analysis, including μCT and RT-qPCR. Addition of PA to the diet had no impact on trabecular bone parameters. However, marrow adiposity was significantly increased in PA-fed mice, and in bone marrow stromal cells isolated from these mice increases in the expression of the lipid storage genes, Plin1 and Cidec, were observed. Thus, as a downstream metabolite of kyn, PA no longer showed kyn's detrimental effects on bone but instead appears to impact energy balance.
AB - Tryptophan is an essential amino acid catabolized initially to kynurenine (kyn), an immunomodulatory metabolite that we have previously shown to promote bone loss. Kyn levels increase with aging and have also been associated with neurodegenerative disorders. Picolinic acid (PA) is another tryptophan metabolite downstream of kyn. However, in contrast to kyn, PA is reported to be neuroprotective and further, to promote osteogenesis in vitro. Thus, we hypothesized that PA might be osteoprotective in vivo. In an IACUC-approved protocol, we fed PA to aged (23-month-old) C57BL/6 mice for eight weeks. In an effort to determine potential interactions of PA with dietary protein we also fed PA in a low-protein diet (8%). The mice were divided into four groups: Control (18% dietary protein), +PA (700 ppm); Low-protein (8%), +PA (700 ppm). The PA feedings had no impact on mouse weight, body composition or bone density. At sacrifice bone and stem cells were collected for analysis, including μCT and RT-qPCR. Addition of PA to the diet had no impact on trabecular bone parameters. However, marrow adiposity was significantly increased in PA-fed mice, and in bone marrow stromal cells isolated from these mice increases in the expression of the lipid storage genes, Plin1 and Cidec, were observed. Thus, as a downstream metabolite of kyn, PA no longer showed kyn's detrimental effects on bone but instead appears to impact energy balance.
KW - Aging
KW - Bone loss
KW - Marrow adipocytes
KW - Stem cells
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U2 - 10.1016/j.exger.2020.110885
DO - 10.1016/j.exger.2020.110885
M3 - Article
C2 - 32088397
AN - SCOPUS:85079875886
VL - 133
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
M1 - 110885
ER -