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The Effects of Fenugreek on Controlling Glucose in Diabetes Mellitus
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Zahra Ayati, Nazli Namazi, Mohammad Hossein Ayati, Seyed Ahmad Emami, Dennis Chang
It is well established that abnormal gut microbiota composition is linked with metabolic disorders, including obesity and diabetes. Galactomannan, the water-soluble polysaccharides in fenugreek gum, has been considered to have the potential to regulate gut microbiota and improve glucose metabolism. In an in vivo study on mice, administration of galactomannan in the diet altered microbiota population in the gut. It also increased adenosine monophosphate-activated protein kinase (AMPK) activation in the liver. AMPK is considered as a regulator of glucose metabolism in the liver, which inhibits the activity of acetyl-coenzyme A carboxylase (ACC) and thus leads to a decrease of lipogenesis (56). A metabonomic study evaluated the underlying antidiabetic mechanism of fenugreek galactomannan in streptozotocin-induced diabetic rats. The results of urine and serum analysis of treated rats revealed that administration of galactomannan modifies a range of biomarkers which are involved in energy metabolism and several other metabolisms, such as phenylalanine, histidine, tryptophan, sphingolipid, glycerophospholipid and arachidonic acid (57). Galactomannan is also suggested to improve and protect the pancreas function. In an in vivo study on diabetic mice, administration of galactomannan protected the pancreas from histological changes (58).
Responses of liver to acute and chronic physical activity
Published in Roy J. Shephard, Physical Activity and the Abdominal Viscera, 2017
Rodent investigations have provided insights into the molecular changes underlying training-induced changes in lipid and lipoprotein metabolism. Training reduces the hepatic levels of two enzymes central to the synthesis of fatty acids: acetyl-coenzyme A carboxylase and fatty acid synthase.[34, 258–260] Regular exercise also down-regulates the hepatic gene and protein content of stearoyl-CoA desaturase-1 (SCD-1), the rate-limiting enzyme in the biosynthesis of saturated-derived monounsaturated fats that are a major constituent of VLDL triglycerides. Further, there is a down-regulation of the microsomal triglyceride transfer protein that plays a key role in the assembly and secretion of VLDL lipoprotein,[261] and training increases levels of hepatic mRNA for the ATP-binding cassette transporter A-1 that plays a vital role in the membrane transport of HDL cholesterol and its remodeling in the plasma.[262]
Metabolic Syndrome and Cardiovascular Disease: Epidemiology, Pathophysiology, and Therapeutic Considerations
Published in P. K. Shah, Risk Factors in Coronary Artery Disease, 2006
Prakash C. Deedwania, Natalia Volkova
Increased visceral adipose tissue is considered to be a major factor responsible for many of the abnormalities associated with metabolic syndrome including insulin resistance. Adipocyte is now recognized as an important secretory organ (Fig. 5) (27). Adipocyte-secreted molecules are called “adipokines.” Adiponectin is one of the adipokines, which is considered to be an important mediator of insulin sensitivity (28). Adiponectin works via activation of the adenosine monophosphate-activated protein kinase in skeletal muscle and liver, leading to phosphorylation of acetyl coenzyme A carboxylase, increased fatty acid oxidation and glucose uptake, reduced fatty acid synthesis, and reduction of molecules involved in gluconeogenesis (29–36). In the absence of metabolic syndrome, these effects result in reduction in triglyceride content in the liver and skeletal muscle and suppression of hepatic glucose production and increase in high density lipoprotein levels (28,36–39).
Toxoplasma gondii infection: novel emerging therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2023
Joachim Müller, Andrew Hemphill
The apicoplast, a specific organelle that is a plant chloroplast homolog, is found in T. gondii and other apicomplexans. Since these plastids harbor specific metabolic pathways absent from mammalian cells, it is natural that not only plastid-borne protein biosynthesis (see above) but also metabolic pathways are regarded as suitable anti-Toxoplasma drug targets [75,100]. Since lipid biosynthesis in plants is plastid-borne and can be targeted by various herbicides, it is straightforward to test such compounds against T. gondii. In vitro tachyzoite proliferation and activity of recombinant Acetyl-Coenzyme A-carboxylase, the first key enzyme of lipid biosynthesis, is inhibited by aryloxyphenoxypropionate herbicides [101]. Moreover, fatty acid synthase II is inhibited by the herbicide haloxyfop [102]. These studies and the generation of a conditional null mutant of the apicoplast acyl carrier protein reveal that apicoplast borne fatty acid biosynthesis is essential for the survival of T. gondii in vitro as well as in vivo [103]. In detail, apicoplast fatty acid synthesis seems to be essential to compounds required for the final step of parasite division [104].
Anti-obesity carbonic anhydrase inhibitors: challenges and opportunities
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
In the last period, CAs were not only considered as being involved in pH regulation/buffering in many cells and tissues, but also as metabolic enzymes16, due to their demonstrated role in several metabolic processes in tumours17,18 and normal cells, including fatty acid biosynthesis and de novo lipogenesis (DNL) – Figure 12,8–12. It has been known for decades that fatty acid biosynthesis and DNL involve both mitochondrial and cytosolic steps, in which several enzymes implicated both in the Krebs cycle as well as DNL, among which pyruvate carboxylase (PC) and acetyl-coenzyme A carboxylase (ACC) use bicarbonate and not CO2 as one of their substrate8–12. In order to achieve the very rapid interconversion between these two species, highly catalytically active CA isoforms (among which CA II in the cytosol13–15 and CA VA/VB in the mitochondria19,20) are necessary to participate21–25. It has been demonstrated already in the 90 s that this is indeed the case, and that inhibition of mitochondrial/cytosolic CAs interferes with fatty acid biosynthesis and DNL in various cells, tissues and animal models21–25.
Multi-drug approaches to NASH: what’s in the development pipeline?
Published in Expert Opinion on Investigational Drugs, 2020
Michael P Johnston, Janisha Patel, Christopher D Byrne
Increased de novo lipogenesis may contribute to dysregulated fatty acid biosynthesis leading to NAFLD/NASH [17]. GS-0976 is an inhibitor of acetyl-coenzyme A carboxylase, the rate-limiting enzyme in fatty acid synthesis. In a phase II placebo-controlled trial, GS-0976 achieved the primary outcome of >30% reduction in hepatic fat content measured by quantification of magnetic resonance imaging-proton density fat fraction [18]. Unfortunately, an unfavorable increase in triglycerides was noted in the treatment arm. There are also currently two registered trials of GS-0976 treatment as part of combination therapy in NASH with both the ASK-1 inhibitor selonsertib and the farnesoid X-activated receptor (FXR) agonist GS-9674 (NCT03449446, NCT03987074). Neither trial is recruiting yet.