Evidence Details for Stat5a
PMID Title Journal Year Abstract
28806763 Genome-wide regulation of electro-acupuncture on the neural Stat5-loss-induced obese mice. PLoS One. 2017 Aug 14;12(8):e0181948. doi: 10.1371/journal.pone.0181948. eCollection 2017. 2017 Acupuncture is reported to be effective in treating obesity related illnesses, but its mechanism is still unclear. To investigate this mechanism we applied electro-acupuncture (EA) in a mouse model of obesity and used RNA-seq to identify molecular consequences. Deletion of the transcription factor STAT5 from neurons (Stat5NKO) led to obesity. Acupuncture, in turn, reduced body weight and the ratio of epididymal white adipose tissue (Epi-WAT) to body weight, and it also decreased plasma concentrations of glucose, triglyceride, and cholesterol. In addition, EA increased cold endurance of Stat5NKO obese mice. EA reversed altered gene expressions in the hypothalamus and Epi-WAT, especially in the hypothalamus in Stat5NKO obese mice. This study provides, for the first time, insight into genomic networks of obesity and their modulation by electro-acupuncture, which in turn reveals potential mechanisms that explain acupuncture-induced weight-loss."

Evidence Sentence: Genome-wide regulation of electro-acupuncture on the neural Stat5-loss-induced obese mice
Evidence Sentence: Deletion of the transcription factor STAT5 from neurons (Stat5NKO) led to obesity.
Evidence Sentence: In addition, EA increased cold endurance of Stat5NKO obese mice.
Evidence Sentence: The results showed that EA significantly reduced the Stat5NKO mice's body weight throughout the duration of treatment (P<0.01)-even as low as that of the Stat5 fl/fl group after two weeks of treatment.
Evidence Sentence: We observed increased food consumption in the Stat5NKO mice compared with the Stat5 fl/fl group, and a subsequent decrease in food consumption following EA treatment in the Stat5 NKO mice during the first two weeks of treatment (P<0.05) that increased again during the last two weeks (Fig 1B).
Evidence Sentence: The results indicated that the Epi-WAT volume in the Stat5NKO group was larger than that in the Stat5fl/fl group, and EA significantly decreased this ratio (P<0.05) (Fig 1C and S3 Fig).
Evidence Sentence: Serum leptin and glucose levels were increased after the deletion of neural Stat5 gene (P<0.01) but were restored to baseline levels similar to those in the Stat5fl/fl mice following EA treatment (Fig 1D).
Evidence Sentence: EA treatment improved energy metabolism and cold tolerance in the Stat5NKO obese mice
Evidence Sentence: In comparison to the Stat5fl/fl group, TC and TG levels in the Stat5NKO group were both significantly elevated (P<0.01) initially but were completely reversed to normal levels after four weeks of EA treatment.
Evidence Sentence: The results showed that Stat5NKO mice's rectal temperatures consistently decreased during the observation period, whereas the decreased temperatures of Stat5fl/fl mice were elevated after 12 hours in the cold room and reverted to the normal level.
Evidence Sentence: We also observed that EA treatment increased rectal temperature of the Stat5NKO mice at the 24-hour mark but did not affect the Stat5fl/fl mice (Fig 1H), indicating that EA treatment could increase the Stat5NKO obese mice's ability to adapt to cold temperatures.
Evidence Sentence: To uncover the potential role of central STAT5 in the development of obesity, as well as the underlying molecular mechanism of EA treatment on obesity, RNA-seq for the hypothalamus and Epi-WAT were performed using next generation high-throughput sequencing.
Evidence Sentence: Compared with the Stat5fl/fl group, 420 genes were differentially expressed in the hypothalamus upon the loss of Stat5 in the central neuron system, in which 80% (336) of the genes were up-regulated and 20% (84) of the genes were down-regulated (Table 1).
Evidence Sentence: Gene ontology (GO) annotation indicated that the up-regulated genes in the hypothalamus of the Stat5NKO mice were mainly expressed in the extracellular region, basement membrane, plasma lipoprotein particle, and cytosol (Fig 2A); and these genes were significantly enriched in 140 biological processes, which were functionally clustered to extracellular matrix organization, response to hormone and insulin stimulus, lipid and saccharide metabolic process, fat cell differentiation, and positive regulation of adaptive and innate immune responses.
Evidence Sentence: From the above analysis, we observed that a large number of genes and functional pathways involved in lipid metabolism, adipogenesis, insulin signaling, and immune system were dependent on the STAT5 molecule in the CNS.
Evidence Sentence: To investigate the extent to which central STAT5 can affect peripheral energy metabolism and adipogenesis, we further measured gene profiling in the Epi-WAT.
Evidence Sentence: EA treatment reversed the abnormal gene expressions in the Stat5 NKO obese mice
Evidence Sentence: Among these genes (Fig 4E), FPKM values of 7 genes, which are associated with immune system and the response to hormone (AY761185, Cst11, Defb20, Defb28, Defb48, Lcn8, Lcn9) were decreased to zero by the deletion of central Stat5, whereas EA treatment reversed their expression levels, and the other 13 genes, such as Gpx5, 9230104L09Rik, Cst12, and Defb25, appeared in the top 40 down-regulated gene list of the Stat5NKO mice (S7 Table).
Evidence Sentence: Altogether, our results suggest that EA treatment can specifically reverse differentially expressed genes via the loss of STAT5 in the central nervous system.
Evidence Sentence: In the Epi-WAT, compared to the Stat5NKO group, 454 DEGs were affected in the Stat5NKO+EA group, in which 361 genes were up-regulated, and 93 genes were down-regulated (Table 1).
Evidence Sentence: Further analysis showed that 201 out of the 361 EA up-regulated genes were on the down-regulated gene list (1106) of the Stat5NKO group.
Evidence Sentence: Additionally, 4 up-regulated genes (Ucp1, Cox7a1, Trfr2 and Ptgr1) as a result of loss of Stat5 in the CNS were also up-regulated by EA treatment, especially the gene encoding UCP1 (uncoupling protein1), which is involved in energy metabolism.
Evidence Sentence: Its FPKM value was nearly zero in the Epi-WAT of the Stat5 fl/fl mice but was increased to 1.51 in the Stat5NKO obese mice, then to 257.39 following EA treatment, becoming the second most EA up-regulated gene (S8 Table).
Evidence Sentence: Although Lep (the gene encoding Leptin) was not included in the top 50 genes down-regulated by EA in the hypothalamus, its FPKM value of the Stat5 fl/fl mice was 4.33, but was decreased from 58.59 to 4.66 in the Stat5NKO+EA group.
Evidence Sentence: Our data thus suggest that EA can reverse the STAT5-dependent genes to their baseline levels to a large extent.
Evidence Sentence: We found that 21 known genes appeared on the list for the hypothalamus of Stat5NKO mice (Fig 5A), and two of them (Prl, Lep) were up-regulated in the hypothalamus of the Stat5NKO group and were decreased by EA, but only one gene (Etv5) was down-regulated due to the loss of Stat5.
Evidence Sentence: In Epi-WAT, 11 genes (Sec16b, Rasal2, Etv5, Slc39a8, Tfap2b, Nfe2l3, Faim2, Npc1, Sim1, Dgkg, and Enpp1) were down-regulated by the loss of Stat5, and two of them (Slc39a8 and Faim2) were significantly up-regulated by EA.
Evidence Sentence: Meanwhile, five genes (Grb14, Pter, Mtch2, Gtf3a, Tmem160) were up-regulated in the Stat5NKO group, and Grb14 was down-regulated by EA.