Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials.

BACKGROUND: Human brown adipose tissue (BAT) activity is associated with lower body fatness and favorable glucose metabolism. Previous studies reported that oral fructose loading induces postprandial fibroblast growth factor 21 (FGF21) secretion. FGF21 is a known inducer of adipose tissue thermogenesis; however, the effects of diet-induced FGF21 secretion on BAT thermogenesis remain to be elucidated. METHODS: The effects of both single load and daily consumption of fructose on BAT activity were examined using a randomized cross-over trial and a 2-week randomized controlled trial (RCT), respectively. In the cross-over trial, 15 young men consumed a single dose of fructose solution or water and then consumed the other on a subsequent day. The RCT enrolled 22 young men, and the participants were allocated to a group that consumed fructose and a group that consumed water daily for 2 weeks. BAT activity was analyzed using thermography with cold exposure. Plasma FGF21 level was determined by enzyme-linked immunosorbent assay. RESULTS: In the cross-over single-load trial, plasma FGF21 levels were significantly increased at 2 h after oral fructose load (p < 0.01); however, there was no significant difference in BAT activity between the fructose load and drinking water. The 2-week RCT revealed that both plasma FGF21 levels and BAT activity were not significantly increased by daily fructose consumption compared to water. Correlation analyses revealed that BAT activity at the baseline and the final measurements were strongly and positively associated with the RCT (r = 0.869, p < 0.001). Changes in BAT activity were significantly and negatively correlated with changes in plasma glucose levels during the 2-week intervention (r = - 0.497, p = 0.022). CONCLUSIONS: Oral fructose load induces a temporary increase in circulating FGF21 levels; however, this does not activate BAT thermogenesis in healthy young men. Further studies are needed to elucidate the effect of endogenous FGF21 on physiological function. TRIAL REGISTRATION: This study is registered with the University Hospital Medical Information Network in Japan (number 000051761, registered 1 August 2023, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052680 ).

Light-induced movement of the LOV2 domain in an Asp720Asn mutant LOV2-kinase fragment of Arabidopsis phototropin 2.

Phototropin, a blue-light receptor protein of plants, triggers phototropic responses, chloroplast relocation, and opening of stomata to maximize the efficiency of photosynthesis. Phototropin is composed of two light-oxygen-voltage sensing domains (LOV1 and LOV2) that absorb blue light and a serine/theroine kinase domain responsible for light-dependent autophosphorylation leading to cellular signaling cascades. Although the light-activated LOV2 domain is primarily responsible for subsequent activation of the kinase domain, it is unclear how conformational changes in the former transmit to the latter. To understand this molecular mechanism in Arabidopsis phototropin 2, we performed small-angle X-ray scattering analysis on a fragment composed of the LOV2 and kinase domains, which contained an Asp720Asn mutation that led to an absence of ATP binding activity. The scattering data were collected up to a resolution of 25 Å. The apparent molecular weight of the fragment estimated from scattering intensities demonstrated that the fragment existed in a monomeric form in solution. The fragment exhibited photoreversible changes in the scattering profiles, and the radii of gyration under dark and blue-light irradiation conditions were 32.4 and 34.8 Å, respectively. In the dark, the molecular shape restored from the scattering profile appeared as an elongated shape of 110 Å in length and 45 Å in width. The homology modeled LOV2 and kinase domains could be fitted to the molecular shape and appeared to make slight contact. However, under blue-light irradiation, a more extended molecular shape was observed. The changes in the molecular shape and radius of gyration were interpreted as a light-dependent positional shift of the LOV2 domain of approximately 13 Å from the kinase domain. Because the region connecting the LOV2 and kinase domains was categorized as a naturally unfolded polypeptide, we propose that the light-activated LOV2 domain triggers conformational changes in the linker region to separate the LOV2 and kinase domains.

[Comparison of radial two-dimensional strain and regional wall motion abnormalities in the patients undergoing off-pump coronary artery bypass grafting].

BACKGROUND: Measurement of myocardial strain by echocardiogram is a novel approach in quantitatively assessing regional ventricular function. We investigated the relationship between left ventricular radial strain and traditional visual assessment of regional wall motion abnormalities. METHODS: We obtained midesophageal short-axis view of the left ventricle at the level of papillary muscles with a transesophageal echocardiography in 32 patients before and after off-pump coronary artery bypass grafting. Off-line analysis of echocardiogram was performed by the two independent observers. A total of 241 segments were divided into 5 grades (normal, mild hypokinesis, severe hypokinesis, akinesis, dyskinesis) according to the grading scale of ASE/SCA recommendations. A peak systolic radial strain was determined for each segment with a two-dimensional tissue-tracking method. RESULTS: The average peak systolic strain was significantly different among normal (38.4 +/- 16.1%), mild hypokinetic (30.8 +/- 14%), and severe hypokinetic (17 +/- 13.1%) segments, while no significant difference was observed between severe hypokinetic and akinetic segments. CONCLUSIONS: Our results suggest that intraoperative strain measurement by transesophageal echocardiography has a good reproducibility and allows quantitative assessment of regional ventricular function during cardiac surgery. However, the peak systolic radial strain may is less capable of differentiating segments with severely impaired wall motion.

Preferable correlation to blastocyst development and pregnancy rates with a new embryo grading system specific for day 3 embryos.

PURPOSE: To investigate the cleavage stage embryo quality by the correlation between the morphological features and blastocyst development rate to develop a new embryo grading system. METHODS: A retrospective analysis, including 216 cycles of cleavage stage embryo transfer and 251 cycles of blastocyst transfer. The correlation with blastocyst development of the embryo cleavage stage, fragmentation and uniformity of blastomeres was evaluated. RESULTS: There were significant differences in the blastocyst development rate between > or =7 cells and < or=6 cells (68.8% vs. 30.7%), <50% fragmentation and > or =50% fragmentation (51.9% vs. 25.7%), and evenly sized blastomeres and unevenly sized blastomeres (48.7% vs. 30.1%) on day 3. The new grading system defined by these 3 parameters showed a preferable correlation to the pregnancy rate. CONCLUSIONS: The new grading system specific for day 3 embryos is useful for the selection of good quality embryos and may improve the pregnancy rate.