It’s possible that a supplement for Neuropeptide Y may not be needed as cold exposure increases Neuropeptide Y levels. But it’s not clear if an increase in Neuropeptide Y will increase height.
“Peripheral neuropeptide Y (NPY) has been reported to regulate bone metabolism and homeostasis, however its potential roles in growth plate chondrogenesis remain unclear. Here, we found that NPY expression decreased during chondrocyte differentiation in vitro and in vivo. NPY was required for chondrocyte proliferation, while in contrast knockdown of NPY facilitated chondrocyte hypertrophic differentiation. {So maybe Neuropeptide Y can keep growth plates open for longer?} Administration of recombinant NPY in rat chondrocytes and metatarsal bones uncoupled the normal proliferation and hypertrophic differentiation during chondrogenesis and thereby inhibited growth plate chondrogenesis and longitudinal bone growth. Remarkably, NPY activated mTORC1 pathway in chondrocytes, whereas attenuation of mTORC1 activity by administration of rapamycin in vitro partially abrogated NPY-mediated effects on chondrocyte proliferation and hypertrophic differentiation. In addition, a combination of Y2R antagonist but not Y1R antagonist with NPY abolished NPY-mediated inhibition of metatarsal growth and growth plate chondrogenesis. Mechanistically, NPY activated Erk1/2 by NPY2R, then phosphorylated ERK1/2 activated mTORC1 to initiate PTHrP expression, which in turn promoted chondrocyte proliferation and inhibited chondrocyte hypertrophic differentiation. In conclusion, our data identified NPY as a crucial regulator of chondrogenesis and may provide a promising therapeutic strategy for skeletal diseases.”
You can potentially buy Neuropeptide Y for lab use. Couldn’t get the full study but here’s another paper on it.
Neuropeptide Y Acts Directly on Cartilage Homeostasis and Exacerbates Progression of Osteoarthritis Through NPY2R
“Neuropeptide Y (NPY) is known to regulate bone homeostasis; however, its functional role as a risk factor during osteoarthritis (OA) remains elusive. In this study, we aim to investigate the direct effect of NPY on degradation of cartilage and progression of OA and explore the molecular events involved. NPY was overexpressed in human OA cartilage accompanied with increased expression of NPY1 receptor (NPY1R) and NPY2 receptor (NPY2R). Stressors such as cold exposure resulted in the peripheral release of NPY from sympathetic nerves{This may explain why people in colder environments are taller}, which in turn promoted upregulation of NPY and NPY2R in articular cartilage in vivo. Intra-articular administration of NPY significantly promoted chondrocyte hypertrophy and cartilage matrix degradation, with a higher OARSI score than that of control mice, whereas inhibition of NPY2R but not NPY1R with its specific antagonist remarkably ameliorated NPY-mediated effects. Moreover, NPY activated mTORC1 pathway in articular chondrocytes, whereas the administration of rapamycin (an mTORC1 inhibitor) in vitro abrogated NPY-mediated effects. Mechanistically, mTORC1 downstream kinase S6K1 interacted with and phosphorylated SMAD1/5/8 and promoted SMAD4 nuclear translocation, resulting in upregulation of Runx2 expression to promote chondrocyte hypertrophy and cartilage degradation. In conclusion, our findings provided the direct evidence and the crucial role of NPY in cartilage homeostasis.”
“peripheral NPY can be also synthesized by osteoblasts, osteocytes, as well as chondrocytes both at embryonic and adult stage”
“the NPY-treated group exhibited more severe OA phenotypes than that of the control group as indicated by significant cartilage degradation and fibrillation together with a higher OARSI score”<-although we don’t know how that will translate to height.
“NPY activated mTORC1 signaling in articular cartilage, which in turn activated SMAD1/5/8 signaling and consequently promoted chondrocyte hypertrophy and cartilage degradation.”
“old exposure stimulates NPY release from sympathetic nerves, and then NPY could enter the blood since NPY-positive sympathetic nerve fibers have been found to be mostly distributed around and within blood vessels. mice exposed in cold water increased circulating NPY.”
Skeletal phenotype of the neuropeptide Y knockout mouse
“lobal deletion of NPY results in a smaller femoral cortical cross-sectional area (-12%) and reduced bone strength (-18%) in male mice. In vitro, NPY-deficient bone marrow stromal cells (BMSCs) showed increase in osteogenic differentiation detected by increases in alkaline phosphatase staining and bone sialoprotein and osteocalcin expression. Despite both sexes presenting with increased adiposity, female mice had no alterations in bone mass, suggesting that NPY may have sex-specific effects on bone”
“wild-type (WT) mice at thermoneutral (29 °C) were compared to mice at room temperature (22 °C) conditions. Interestingly, bone mass was lower in cold-stressed WT mice with significant reductions in femoral bone mineral content (− 19%) and bone volume (− 13%).”
Magnitude and pattern of compensatory growth in rats after cold exposure
“It is a common observation that normal growth is affected or suppressed in young individuals by environmental adversities and physical disturbances. On the other hand, when health or favorable conditions are restored, the tempo of growth promptly accelerates as if the individual is trying to make up for the growth debt incurred.”
“Growth retardation during the single cold exposure period, and prompt compensatory growth after return to the warm environment, occurred in both the tail and the body, and in the younger A as well as the older B rats. During the 2-week periods of cold exposure, tail gain of the A rats was only about 30 % of that of the warm controls (W2), while that of the B rats averaged about 50 %. Likewise, the rapid compensatory growth in tail length during the 2 weeks immediately after the end of cold exposure was more prominent in the A than in the B rats: the tail gain in the A
rats averaged around 145 % of that of the controls in contrast to 130 % in the B rats. Not only was the compensation greater in the A rats, but the compensatory period (period of significantly faster growth) was longer also, extending over 8 weeks (from 3rd to 10th), in contrast to 4 weeks (from 6th to 10th) in the B rats. By the end of the 10th week the tail length of A and B rats was not significantly shorter than that of the W2 group”
Uncoupling protein-1 is protective of bone mass under mild cold stress conditions
“UCP-1 is critical for protecting bone mass in mice under conditions of permanent mild cold stress for this species (22 °C). UCP-1−/− mice housed at 22 °C showed significantly lower cancellous bone mass, with lower trabecular number and thickness, a lower bone formation rate and mineralising surface, but unaltered osteoclast number, compared to wild type mice housed at the same temperature. UCP-1−/− mice also displayed shorter femurs than wild types, with smaller cortical periosteal and endocortical perimeters. Importantly, these altered bone phenotypes were not observed when UCP-1−/− and wild type mice were housed in thermo-neutral conditions (29 °C), indicating a UCP-1 dependent support of bone mass and bone formation at the lower temperature. Furthermore, at 22 °C UCP-1−/− mice showed elevated hypothalamic expression of neuropeptide Y (NPY) relative to wild type, which is consistent with the lower bone formation and mass of UCP-1−/− mice at 22 °C caused by the catabolic effects of hypothalamic NPY-induced SNS modulation.”
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