Biology subjects

Zhang, K. X.

Publications and source records attributed to Zhang, K. X..

3 recordsLinked to original sources

bioRxiv2022

High fat diet initiates rapid adaptation of the intestine

While the systemic impacts of overnutrition are well-known to cause obesity and metabolic syndrome over the course of months, the immediate adaptive response of the intestinal epithelium to dietary changes remains poorly understood. Here we used physiological metrics and single cell analyses to interrogate the adaptive response of intestinal epithelial cells when moved to a high fat diet (HFD). Within 1 day of HFD exposure, mice exhibited altered feeding behavior, an increase in energy expenditure and an increase in intestinal epithelial proliferation. Single cell transcriptional analysis demonstrated several acute cellular changes on day 1, including a cell-stress response in intestinal crypts, de-granularization of Paneth cells, and a shift towards fatty acid cellular metabolism. By 3 days of HFD, there was an emergence of uncommitted progenitors with a transcriptional profile indicative of a shift from secretory populations and towards an absorptive fate. In enterocytes, genes regulating lipid transport and absorption increased over the first 3 days which paralleled a functional increase in lipid absorption in vivo over the course of 7 days on HFD. These findings demonstrate that intestinal epithelial cell populations respond rapidly to changes in diet through initial changes in cellular function followed by a shift in cellular composition.

cell biology↗

bioRxiv2019

Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

Almost all life forms can decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are interpreted as images, and the circadian system, where light entrains a physiological clock. Here we describe a local, non-visual light response in mice that employs encephalopsin (OPN3, a 480 nm, blue light responsive opsin) to regulate the function of adipocytes. Germ line null and adipocyte-specific conditional null mice show a deficit in thermogenesis that is phenocopied in mice under blue-light deficient conditions. We show that blue light stimulation of adipocytes activates hormone sensitive lipase, the rate limiting enzyme in the lipolysis pathway, and that this is OPN3-dependent. Opn3 adipocyte conditional null mice also use reduced levels of fat mass when fasted and cold exposed further suggesting a lipolysis deficit. These data suggest the hypothesis that in mice, a local, OPN3-dependent light response in adipocytes is a mechanism for regulation of energy homeostasis.

physiology↗

bioRxiv2018

An adipocyte light-Opsin 3 pathway regulates the circadian clock and energy balance.

Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are processed into virtual images, and the circadian system, where light entrains a physiological clock. Here we describe a pathway in mice that employs encephalopsin (OPN3, a 480 nm light responsive opsin) to mediate light responses in murine adipocytes. The adipocyte light-OPN3 pathway regulates neonatal growth in mice and is required for at least three important functions including (1) photoentrainment of a local circadian clock, (2) extracellular matrix deposition, and (3) regulation of mitochondrial content and the proportion of \"brite\" adipocytes. Furthermore, we show that the light-OPN3 pathway is required for normal levels of uncoupling protein 1 (UCP1) in white and brown adipose tissue. Consequently, neonatal Opn3 germ-line and adipocyte-conditional null mice show a reduced ability to maintain their body temperature under cold stress. This was also observed in wild-type mice deprived of blue light. We hypothesize that the adipocyte light-OPN3 pathway provides a dynamically responsive, circadian clock-integrated mechanism for regulating adipocyte function and in turn directing metabolism to thermogenesis rather than anabolism. These data indicate an important role for peripheral light sensing in mammals and may have broad implications for human health given the unnatural lighting conditions in which we live.

physiology↗