The storage of fat within lipid droplets (LDs) of adipocytes is critical for whole-body health. Acute fatty acid (FA) uptake by differentiating adipocytes leads to the formation of at least two LD classes marked by distinct perilipins (PLINs). How this LD heterogeneity arises is an important yet unresolved cell biological problem.
View Article and Find Full Text PDFThe small intestine displays marked anatomical and functional plasticity that includes adaptive alterations in adult gut morphology, enteroendocrine cell profile and their hormone secretion, as well as nutrient utilization and storage. In this Perspective, we examine how shifts in dietary and environmental conditions bring about changes in gut size, and describe how the intestine adapts to changes in internal state, bowel resection and gastric bypass surgery. We highlight the critical importance of these intestinal remodelling processes in maintaining energy balance of the organism, and in protecting the metabolism of other organs.
View Article and Find Full Text PDFIntestinal surface changes in size and function, but what propels these alterations and what are their metabolic consequences is unknown. Here we report that the food amount is a positive determinant of the gut surface area contributing to an increased absorptive function, reversible by reducing daily food. While several upregulated intestinal energetic pathways are dispensable, the intestinal PPARα is instead necessary for the genetic and environment overeating-induced increase of the gut absorptive capacity.
View Article and Find Full Text PDFBackground: Body weight (BW) loss is prevalent in patients with pancreatic cancer (PC). Gut microbiota affects BW and is known to directly shape the host immune responses and antitumor immunity. This pilot study evaluated the link between gut microbiota, metabolic parameters and inflammatory/immune parameters, through the fecal material transplantation (FMT) of PC patients and healthy volunteers into germ-free (GF) mice.
View Article and Find Full Text PDFAutoimmunity is energetically costly, but the impact of a metabolically active state on immunity and immune-mediated diseases is unclear. Ly6C monocytes are key effectors in CNS autoimmunity with an elusive role in priming naive autoreactive T cells. Here, we provide unbiased analysis of the immune changes in various compartments during cold exposure and show that this energetically costly stimulus markedly ameliorates active experimental autoimmune encephalomyelitis (EAE).
View Article and Find Full Text PDFAdipose tissues play an essential role in regulating the metabolic homeostasis and can be found in almost all parts of the body. Excessive adiposity leads to obesity and can contribute to metabolic and other disorders. Adipocytes show remarkable plasticity in their function, which can be pushed toward energy storage, or energy expenditure-a `browning' of fat.
View Article and Find Full Text PDFMicrobial functions in the host physiology are a result of the microbiota-host co-evolution. We show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss.
View Article and Find Full Text PDFBrown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice.
View Article and Find Full Text PDFExon splicing enhancers (ESEs) overlap with amino acid coding sequences implying a dual evolutionary selective pressure. In this study, we map ESEs in the placental alkaline phosphatase gene (ALPP), absent in the corresponding exon of the ancestral tissue-non-specific alkaline phosphatase gene (ALPL). The ESEs are associated with amino acid differences between the transcripts in an area otherwise conserved.
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