Extended Data Fig. 8: Inhibition of urinary fluid flow impairs expression of enzymes involved in lipid metabolism.
(a-h) Mice subjected to UUO or a sham operation and fasted during the same period of time were euthanized 24 h after surgery. (a) Images of kidney sections subjected to immunohistochemistry for LDs (red) and LTL (green). Scale bars, 10 μm. Representative images from n = 5 (sham) and =6 (UUO) different mice (b–h) Quantitative RT–qPCR measurements of b) Ppara, c) Ppargc1a, d) Mcad, e) Cpt1b f) Tim23 g) Nrf1 h) Nrf2 in UUO and sham-operated mice. Data were normalized with respect to Gapdh and are presented as fold increases. Data are means ± SEM, n = 5 and 6 for sham and UUO respectively. The statistical significance of b–h) was calculated by a two-tailed t-test. (i) Model of how the primary cilium and lipophagy control metabolic fitness in proximal tubule kidney epithelial cells in response to fluid flow-induced shear stress. Shear stress induces primary cilia-dependent OXPHOS stimulation to ensure ATP production and support energy-consuming cellular processes such as glucose reabsorption, gluconeogenesis, and cytoskeleton remodeling. This metabolic adaptation is dependent on AMPK and is characterized by the stimulation of two pathways: the induction of lipophagy to produce fatty acids and the increase of mitochondrial biogenesis. The statistical significance was calculated by a two-tailed t-test. Data are available as source data.
