Regulation of metabolic health by dietary histidine in mice.

Low-protein (LP) diets are associated with a decreased risk of diabetes in humans, and promote leanness and glycaemic control in both rodents and humans. While the effects of an LP diet on glycaemic control are mediated by reduced levels of the branched-chain amino acids, we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to an LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces the weight gain of young, lean male mice, reducing both adipose and lean mass without altering glucose metabolism, and rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity. This normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. Surprisingly, the effects of histidine restriction do not require the energy balance hormone Fgf21. Histidine restriction that was started in midlife promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary histidine may be a translatable option for the treatment of obesity. KEY POINTS: Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan. Restriction of specific individual essential amino acids can recapitulate the benefits of PR. Reduced histidine promotes leanness and increased energy expenditure in male mice. Reduced histidine does not extend the lifespan of mice when begun in midlife. Dietary levels of histidine are positively associated with body mass index in humans.

Second generation slit-based photoacoustic tomography system for vascular imaging in human.

Slit-based photoacoustic tomography is a newly developed technique that improves the elevation numerical aperture of a linear array through acoustic diffraction. The slit, placed at the acoustic focus of a linear array, effectively forms an array of virtual detectors with high receiving angle, which subsequently improves the elevation resolution. However, due to the complex implementation, our original system could only image phantoms and sacrificed animals. In this report, the system has been significantly improved. In particular, we designed a slit holder that can be directly mounted to the transducer array for easy adjustment of slit width and simultaneous scanning of both the array and the slit. To enlarge the imaging field of view, we replaced the single circular optical fiber bundle with a bifurcated line fiber bundle which moved simultaneously with the array and the slit. The data acquisition system has also been updated to double the imaging speed. With these improvements, the new system can image a 3.8 × 4 cm2 region within 40 seconds and the object only needs to be coupled through ultrasound gel. We successfully used the system to image vasculatures in the palm and forearm of human volunteers. 3D palm vascular image of human palm.