Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is crucial for nutrient-dependent carbohydrate response element-binding protein (ChREBP) activation in adipocytes and plays a key role, particularly in females, in the storage of newly synthesized fatty acids in adipose tissue. The data indicate that adipocyte ACLY is important in females for the systemic handling of dietary carbohydrates and for the preservation of metabolic homeostasis

The effect of pH treatment and refrigerated storage on natural colourant preparations (betacyanins) from red pitahaya and their potential application in yoghurt

© 2017 Elsevier Ltd The present study investigated the effects of pH (pH 3, 4, 5 and 6) treatment and refrigerated storage at 4 °C on the stability of colourant preparations from red pitahaya and compared to a commercial colourant preparations from red beet, E-162. The potential of using colourant preparations from red pitahaya in yoghurt and compared to E-162 was also investigated. Immediately after pH treatment, the highest percentage of reduction of betacyanin was observed at pH 3. The loss of betacyanin content in yoghurts containing colourant preparations from red pitahaya and E-162 over 14-days of refrigerated storage was 1.0± 0% and 1.6± 0.1%, respectively. Syneresis in yoghurt containing colourant preparations from red pitahaya and E-162 were lower than that of plain yoghurt. The addition of betacyanins from red pitahaya or E-162 increased the free radical scavenging activity in yoghurts. The total microbial counts of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus in yoghurts containing colourant preparations from red pitahaya and E-162 were in the 10 8 –10 9  CFU/mL range. The colour acceptability of yoghurt containing colourant preparation from red pitahaya was similar with E-162 and a commercial strawberry flavoured yoghurt suggesting its potential application as a natural functional colourant

Adult neural stem cell activation in mice is regulated by the day/night cycle and intracellular calcium dynamics.

Neural stem cells (NSCs) in the adult brain transit from the quiescent state to proliferation to produce new neurons. The mechanisms regulating this transition in freely behaving animals are, however, poorly understood. We customized in vivo imaging protocols to follow NSCs for several days up to months, observing their activation kinetics in freely behaving mice. Strikingly, NSC division is more frequent during daylight and is inhibited by darkness-induced melatonin signaling. The inhibition of melatonin receptors affected intracellular Ca2+ dynamics and promoted NSC activation. We further discovered a Ca2+ signature of quiescent versus activated NSCs and showed that several microenvironmental signals converge on intracellular Ca2+ pathways to regulate NSC quiescence and activation. In vivo NSC-specific optogenetic modulation of Ca2+ fluxes to mimic quiescent-state-like Ca2+ dynamics in freely behaving mice blocked NSC activation and maintained their quiescence, pointing to the regulatory mechanisms mediating NSC activation in freely behaving animals

Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues.

Fatty acid synthase (FASN) predominantly generates straight-chain fatty acids using acetyl-CoA as the initiating substrate. However, monomethyl branched-chain fatty acids (mmBCFAs) are also present in mammals but are thought to be primarily diet derived. Here we demonstrate that mmBCFAs are de novo synthesized via mitochondrial BCAA catabolism, exported to the cytosol by adipose-specific expression of carnitine acetyltransferase (CrAT), and elongated by FASN. Brown fat exhibits the highest BCAA catabolic and mmBCFA synthesis fluxes, whereas these lipids are largely absent from liver and brain. mmBCFA synthesis is also sustained in the absence of microbiota. We identify hypoxia as a potent suppressor of BCAA catabolism that decreases mmBCFA synthesis in obese adipose tissue, such that mmBCFAs are significantly decreased in obese animals. These results identify adipose tissue mmBCFA synthesis as a novel link between BCAA metabolism and lipogenesis, highlighting roles for CrAT and FASN promiscuity influencing acyl-chain diversity in the lipidome

Betalains: Natural plant pigments with potential application in functional foods

Betalains are plant derived natural pigments that are presently gaining popularity for use as natural colorants in the food industry. The growing interest of consumers in the aesthetic, nutritional and safety aspects of food has increased the demand for natural pigments such as betalains to be used as alternative colorants in food products. Although betalains from red beetroot are one of the most widely used food colorant, betalains are not as well studied as compared to other natural pigments such as anthocyanins, carotenoids or chlorophylls. This paper reviews the pharmacological properties, such as antioxidant, anti-cancer, anti-lipidemic and antimicrobial activity of betalains derived from sources such as red beetroot, amaranth, prickly pear and red pitahaya, for potential application as functional foods

Non-canonical mTORC2 Signaling Regulates Brown Adipocyte Lipid Catabolism through SIRT6-FoxO1

mTORC2 controls glucose and lipid metabolism, but the mechanisms are unclear. Here, we show that conditionally deleting the essential mTORC2 subunit Rictor in murine brown adipocytes inhibits de novo lipid synthesis, promotes lipid catabolism and thermogenesis, and protects against diet-induced obesity and hepatic steatosis. AKT kinases are the canonical mTORC2 substrates; however, deleting Rictor in brown adipocytes appears to drive lipid catabolism by promoting FoxO1 deacetylation independently of AKT, and in a pathway distinct from its positive role in anabolic lipid synthesis. This facilitates FoxO1 nuclear retention, enhances lipid uptake and lipolysis, and potentiates UCP1 expression. We provide evidence that SIRT6 is the FoxO1 deacetylase suppressed by mTORC2 and show an endogenous interaction between SIRT6 and mTORC2 in both mouse and human cells. Our findings suggest a new paradigm of mTORC2 function filling an important gap in our understanding of this more mysterious mTOR complex.Fil: Jung, Su Myung. University Of Massachusetts Medical School; Estados UnidosFil: Hung, Chien Min. University Of Massachusetts Medical School; Estados UnidosFil: Hildebrand, Samuel R.. University Of Massachusetts Medical School; Estados UnidosFil: Sanchez Gurmaches, Joan. University Of Massachusetts Medical School; Estados UnidosFil: Martinez Pastor, Barbara. Harvard Medical School; Estados UnidosFil: Gengatharan, Jivani M.. University of California; Estados UnidosFil: Wallace, Martina. University of California; Estados UnidosFil: Mukhopadhyay, Dimpi. University Of Massachusetts Medical School; Estados UnidosFil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Luciano, Amelia K.. University Of Massachusetts Medical School; Estados UnidosFil: Hsiao, Wen Yu. University Of Massachusetts Medical School; Estados UnidosFil: Tang, Yuefeng. University Of Massachusetts Medical School; Estados UnidosFil: Li, Huawei. University Of Massachusetts Medical School; Estados UnidosFil: Daniels, Danette L.. No especifíca;Fil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Metallo, Christian M.. University of California; Estados UnidosFil: Guertin, David A.. University Of Massachusetts Medical School; Estados Unido

Insulin-regulated serine and lipid metabolism drive peripheral neuropathy.

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3-7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8-10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10-14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically