Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely: 1. the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport), 2. the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recently 3. the stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes). This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity

Effects of adaptation to sea water, 170% sea water and to fresh water on activities and subcellular distribution of branchial Na + −K + -ATPase, low- and high affinity Ca ++ -ATPase, and ouabain-insensitive ATPase in Gillichthys mirabilis

1. Branchial activities of Na + −K + -ATPase, ouabain-insensitive ATPase, (Mg ++ -ATPase) and Ca ++ -ATPase were measured in Gillichthys mirabilis after adaptation to salinities ranging from 170% SW to FW. Stabilities of these activities against freezing and deoxycholate solubilization and the temperature-dependence of activity rates were also investigated. Subcellular distribution and some kinetic properties of these activities, and of SDH were compared in branchial tissues of fish adapted to 170% SW and to FW.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47126/1/360_2004_Article_BF00782593.pd

Toxicity of CeO2 Nanoparticles – The Effect of Nanoparticle Properties

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Artificial intelligence-driven radiomics study in cancer : the role of feature engineering and modeling

202404 bcchVersion of RecordOthersNational Natural Science Foundation of China; Shenzhen Basic Research Program ; Shenzhen‑Hong Kong‑Macau S&T Program (Category C); Mainland‑Hong Kong Joint Funding Scheme (MHKJFS); Project of Strategic Importance Fund; Projects of RISA, Hong Kong Polytechnic University; Natural Science Foundation of Jiangsu Province; Provincial and Ministry Co‑constructed Project of Henan Province Medical Science and Technology Research; Henan Province Key R&D and Promotion Project (Science and Technology Research); Natural Science Foundation of Henan Province; Henan Province Science and Technology ResearchPublishedC

Development of obesity in transgenic mice after genetic ablation of brown adipose tissue.

Brown adipose tissue, because of its capacity for uncoupled mitochondrial respiration, has been implicated as an important site of facultative energy expenditure. This has led to speculation that this tissue normally functions to prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and hypertrophy. Here we have used a transgenic toxigene approach to create two lines of transgenic mice with primary deficiency of brown adipose tissue. At 16 days, both lines have decreased brown fat and obesity. In one line, brown fat subsequently regenerates and obesity resolves. In the other line, the deficiency persists and obesity, with its morbid complications, advances. Obesity develops in the absence of hyperphagia, indicating that brown fat deficient mice have increased metabolic efficiency. As obesity progresses, transgenic animals develop hyperphagia. This study supports a critical role for brown adipose tissue in the nutritional homeostasis of mice