Diurnal changes in the murine small intestine are disrupted by obesogenic Western Diet feeding and microbial dysbiosis

Intestinal functions demonstrate circadian rhythms thought to be entrained, in part, by an organisms’ intrinsic feeding and fasting periods as well as by the intestinal microbiome. Circadian disruption as a result of ill-timed nutrient exposure and obesogenic feeding poses an increased risk to disease. As such, the aim of this study was to assess the relationships between dietary timing, composition, and the microbiome with regard to rhythmic small intestinal structure and mucosal immunity. Rodent chow (RC)-mice exhibited time-dependent increases in small intestinal weight, villus height, and crypt depth as well as an increased proportion of CD8αα+ cells and concomitant decrease in CD8αβ+ cells at the onset of the feeding period (p < 0.05–0.001). Western diet (WD)-animals displayed disrupted time-dependent patterns in intestinal structure and lymphocyte populations (p < 0.05–0.01). Antibiotic-induced microbial depletion abrogated the time- and diet-dependent patterns in both RC- and WD-mice (p < 0.05–0.001). However, although germ-free-mice displayed altered rhythms, fecal microbial transfer from RC-mice was generally unsuccessful in restoring structural and immune changes in these animals. This study shows that adaptive changes in the small intestine at the onset of the feeding and fasting periods are disrupted by WD-feeding, and that these changes are dependent, in part, on the intestinal microbiome.

Hyperpolarized Dihydroxyacetone Is a Sensitive Probe of Hepatic Gluconeogenic State

Type II diabetes and pre-diabetes are widely prevalent among adults. Elevated serum glucose levels are commonly treated by targeting hepatic gluconeogenesis for downregulation. However, direct measurement of hepatic gluconeogenic capacity is accomplished only via tracer metabolism approaches that rely on multiple assumptions, and are clinically intractable due to expense and time needed for the studies. We previously introduced hyperpolarized (HP) [2-13C]dihydroxyacetone (DHA) as a sensitive detector of gluconeogenic potential, and showed that feeding and fasting produced robust changes in the ratio of detected hexoses (6C) to trioses (3C) in the perfused liver. To confirm that this ratio is robust in the setting of treatment and hormonal control, we used ex vivo perfused mouse livers from BLKS mice (glucagon treated and metformin treated), and db/db mice. We confirm that the ratio of signal intensities of 6C to 3C in 13C nuclear magnetic resonance spectra post HP DHA administration is sensitive to hepatic gluconeogenic state. This method is directly applicable in vivo and can be implemented with existing technologies without the need for substantial modifications.

The critical role of FXR is associated with the regulation of autophagy and apoptosis in the progression of AKI to CKD

Autophagy is important for cells to break down and recycle cellular proteins, remove damaged organelles, and especially, for recovery from acute kidney injury (AKI). Despite research on the role and cellular mechanism of autophagy in AKI, the role of autophagy in the progression to chronic kidney disease (CKD) remains poorly understood. Here, using farnesoid X receptor (FXR) knockout (KO) mice, we determined whether FXR prevents the progression of AKI to CKD after renal ischemic-reperfusion (such as I/R) injury through the regulation of renal autophagy and apoptosis. FXR regulated genes that participate in renal autophagy under feeding and fasting conditions, such as hepatic autophagy, and the activation of FXR by agonists, such as GW4064 and INT-747, attenuated the increased autophagy and apoptosis of hypoxia-induced human renal proximal tubule epithelial (HK2) cells. The expression levels of autophagy-related and apoptosis-related proteins in FXR KO mice were increased compared with those in wild-type (WT) mice. We also showed that the increase in reactive oxidative species (ROS) in hypoxia-treated HK2 cells was attenuated by treatment with FXR agonist or by FXR overexpression, and that the level of ROS was elevated in FXR-deficient cells and mice. At 28 days after I/R injury, the autophagy levels were still elevated in FXR KO mice, and the expression levels of fibrosis-related proteins and ROS deposits were higher than those in WT mice. In conclusion, the regulation of renal autophagy and apoptosis by FXR may be a therapeutic target for the early stages of kidney damage, and the progression of AKI to CKD.

Fattening chips: hypertrophy, feeding, and fasting of human white adipocytes in vitro

Micropatterned adipocytes are grown to adult cell sizes in vitro on a nanofiber network.

Feeding and Fasting Bodies

Treating women as helpless victims of social conventions or as neoliberal, postmodern subjects to understand “food femininities” obscures the fact that bodies are situated in social hierarchies. Social functions and roles tied to the female body bring about difference in eating and dieting practices. This chapter applies Bourdeusian analysis to the dieting and religious fasting practices of forty-eight women in the rapidly neoliberalizing city of Kolkata, India, to show how structurally rooted dispositions inform rules of engagement surrounding eating. Dieting and religious fasting, though simultaneously self-gratifying and strenuous, took on very different meanings depending on how they enabled women to seek recognition and meaning in their daily lives. The women who dieted projected their bodies onto the public sphere to secure the benefits that the new economic order could bestow, while familial fasts were an embodiment of the collective, material struggles less privileged women encountered on a daily basis.