Obesity and its associated comorbidities (e.g., diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually1 and are among the most prevalent and challenging conditions confronting the medical profession2,3. Neurotensin (NT), a 13-amino acid peptide predominantly localized in specialized enteroendocrine (EE) cells of the small bowel4 and released by fat ingestion5, facilitates fatty acid (FA) translocation in rat intestine6, and stimulates growth of various cancers7; the effects of NT are mediated through three known NT receptors (NTR1, 2 and 3)8. Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality9; however, a role for NT as a causative factor in these diseases is unknown. Here, we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates FA absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3/sortilin. Consistent with the findings in mice, expression of NT in Drosophila midgut EE cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.

3D printing of reduced graphene oxide (rGO) nanowires is realized at room temperature by local growth of GO at the meniscus formed at a micropipette tip followed by reduction of GO by thermal or chemical treatment. 3D rGO nanowires with diverse and complicated forms are successfully printed, demonstrating their ability to grow in any direction and at the selected sites.

Organic electronics increasingly impacts our everyday life with a variety of devices such as displays for TV or mobile appliances, smart cards and radio-frequency identifi cation (RFID) tags. [ 1 , 2 ] This blossoming domain could greatly profi t from effective ways to fabricate conducting or semiconducting organic nanowires. [ 3 ] Specifi cally, the three-dimensional (3D) and individual integration of each nanowire is essential [ 4 ] for many new device concepts, but so far this was not possible. Here we show the demonstration of accurate and versatile 3D direct writing of conducting polymer nanowires based on guiding a monomer meniscus by pulling a micropipette during oxidative polymerization. This is an important step for organic electronic integration with high density and enhanced freedom in circuit design.Conducting polymers such as polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) are very interesting materials because they combine tunable electrical transport characteristics and excellent mechanical properties. [ 5 ] In particular, conducting polymer nanowires are quite important for a broad range of nanodevices such as fi eld effect transistors, [ 3 ] bio-and chemical sensors, [ 6 , 7 ] and non-volatile memories. [ 8 ] Such nanowires are fabricated by soft lithography, [ 9 , 10 ] dip-pen lithography [ 11 ] and electrospinning. [ 12 ] However, these methods are still limited to in-plane patterning of low-aspect-ratio nanowires, whereas for advanced applications 3D patterning is essential.Direct ink writing and probe-based drawing are used for 3D wire patterning. The fi rst method, based on the extrusion of concentrated ink through a nozzle, was applied for 3D microfabrication with metals, oxides, and polymers. [13][14][15][16] However, bringing the wire diameter below micrometer-level is not easy due to the size and concentration of the ink particles. Probe-based drawing can fabricate polymer nanowires. [ 17 ] However, high-density integration is limited by the large pre-deposited polymer droplet (a few tens to hundreds of micrometers).An alternate technique for 3D electrodeposition was recently developed: writing nanowires with a nanoscale electrolyte meniscus. [ 18 , 19 ] This method was so far demonstrated for 3D metallic nanowires but not for conducting polymers.Here we show that this type of technique can in fact be used for conducting polymers offering high accuracy, excellent versatility and marked advantages with respect to alternate solutions. In essence, we obtained a stretched monomer meniscus by pulling a micropipette fi lled with a Py solution, exploiting oxidative polymerization in air. The wire radius so produced was accurately controlled down to ∼ 50 nm by tuning the pulling speed.The technique was successfully tested with specifi c focus on essential features for advanced organic nanodevice integration. Specifi cally, we produced dense arrays of different types of freestanding nanocomponents: straight wires, complex-shape wires, branche...

Fatty acid synthase (FASN), a lipogenic enzyme, is upregulated in colorectal cancer (CRC). Increased de novo lipid synthesis is thought to be a metabolic adaptation of cancer cells that promotes survival and metastasis; however, the mechanisms for this phenomenon are not fully understood. We show that FASN plays a role in regulation of energy homeostasis by enhancing cellular respiration in CRC. We demonstrate that endogenously synthesized lipids fuel fatty acid oxidation, particularly during metabolic stress, and maintain energy homeostasis. Increased FASN expression is associated with a decrease in activation of energy-sensing pathways and accumulation of lipid droplets in CRC cells and orthotopic CRCs. Immunohistochemical evaluation demonstrated increased expression of FASN and p62, a marker of autophagy inhibition, in primary CRCs and liver metastases compared to matched normal colonic mucosa. Our findings indicate that overexpression of FASN plays a crucial role in maintaining energy homeostasis in CRC via increased oxidation of endogenously synthesized lipids. Importantly, activation of fatty acid oxidation and consequent downregulation of stress-response signaling pathways may be key adaptation mechanisms that mediate the effects of FASN on cancer cell survival and metastasis, providing a strong rationale for targeting this pathway in advanced CRC.