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Mitigation of Obesity: A Phytotherapeutic Approach
Published in Amit Baran Sharangi, K. V. Peter, Medicinal Plants, 2023
A.B. Sharangi, Suddhasuchi Das
Any undesirable imbalance between energy intake and expenditure results in obesity. When dietary energy intake exceeds energy spending, surplus energy is converted to triglyceride which is stored in adipose tissue, thereby increasing body fat and causing weight gain. Obesity is assessed by means of body mass index (BMI) which is obtained by dividing the body weight (kg) with the square of height (m). A value of and over 30 kg/m indicates obesity. Nearly 1.9 billion adults (18 years or more) around the world are overweight and about 600 million of them are clinically obese. That is why obesity is recognized as one of the major health related threats throughout the globe (WHO, 2020). This malady, initially a concern for higher-income countries, is now on the rise in low- and middle-income countries also, especially in urban areas. The characteristic symptom of obesity is an increase in adipose cell size as quantified by the amount of fat accumulation at the cytoplasm of adipocytes (Devlin et al., 2000). Enzymes namely fatty acid synthase, lipoprotein lipase and adipocyte fatty acid-binding protein controls this metabolic change in the adipocytes (Rosen et al., 2000).
Fatty Liver Disease
Published in David Heber, Zhaoping Li, Primary Care Nutrition, 2017
Continuous fructose ingestion may impose a metabolic burden on the liver through the induction of fructokinase and fatty acid synthase. In the liver, fructose is metabolized to fructose-1-phosphate by fructokinase, which consumes ATP (Lim et al. 2010; Lustig 2010). As a consequence, a massive incorporation of fructose into liver metabolism can lead to high levels of metabolic stress via ATP depletion. In an experimental study in the rat (Koo et al. 2008), it was shown that fructose-induced fructokinase hyperexpression in the liver can be reduced (by 0.6-fold) by the hydroxymethyl-glutaryl-coenzyme A reductase inhibitor atorvastatin. Of note, clinical studies have shown that atorvastatin can improve liver injury in NAFLD patients with hyperlipidemia (Teff et al. 2004; Lê and Tappy 2006). Fatty acid synthase catalyzes the last step in the fatty acid biosynthetic pathway and is a key determinant of the maximal capacity of the liver to synthesize fatty acids by de novo lipogenesis (D’Angelo et al. 2005). In a clinical study, increased fructose consumption in patients with NAFLD was associated with hyperexpression of hepatic mRNA for fatty acid synthase, suggesting that this molecular derangement could play a crucial role in fructose-induced fatty liver infiltration (Ackerman et al. 2005).
Biology of microbes
Published in Philip A. Geis, Cosmetic Microbiology, 2006
Synthesis of lipids. Fatty acid synthesis is catalyzed with fatty acid synthetase using acetyl-CoA and malonyl-CoA as the substrates and NADPH as the reductant. Malonyl-CoA comes from an ATP-driven carboxylation (addition of CO2) of acetyl-CoA that comes from glycolysis. Both acetate and malonate are transferred from coenzyme A to the sulfhydryl group of the acyl carrier protein (ACP) that carries the growing fatty acid chain during synthesis. The synthetase adds two carbons at a time to the carboxyl end of the growing fatty acid chain in a two-stage process. First, malonyl-ACP reacts with a fatty acyl-ACP and yields CO2 and a fatty acyl-ACP that is now two carbons longer. Glycerol can be esterified to fatty acids to result in phosphatidic acid and then to phospholipids that are essential to membrane function.
Attenuation of obesity related inflammation in RAW 264.7 macrophages and 3T3-L1 adipocytes by varanadi kashayam and identification of potential bioactive molecules by UHPLC-Q-Orbitrap HRMS
Published in Archives of Physiology and Biochemistry, 2023
J. U. Chinchu, Mohind C. Mohan, B. Prakash Kumar
Obesity is a major health problem characterised by excessive body fat accumulation through an imbalance between energy intake and consumption and is responsible for developing type 2 diabetes, coronary heart disease and certain cancers (Guyenet and Schwartz 2012). Obesity is mainly associated with an increase in white adipose tissue mass through activation of adipogenesis and increased deposition of cytoplasmic triglycerides (Frigolet et al. 2008). Adipogenesis is a highly regulated process in which undifferentiated fibroblasts (preadipocytes) become mature adipocytes and is regulated by an elaborate network of transcription factors including CCAAT/enhancer-binding protein (C/EBP) and peroxisome proliferator-activated receptor-γ (PPAR-γ) (Yu et al. 2014). C/EBP-α and PPAR-γ work cooperatively in inducing the adipocyte differentiation process and promote the expression of fatty acid synthase (FAS) to trigger the synthesis and accumulation of triglyceride (TG) in mature adipocyte (Farmer 2006). Therefore, adipogenesis inhibition by downregulating adipogenic transcriptional factor expressions is critical for achieving an anti-obesity effect.
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].
Fatty acid synthase: a druggable driver of breast cancer brain metastasis
Published in Expert Opinion on Therapeutic Targets, 2022
Here, we revisit the notion of metabolic-metastasis speciation [22–24], which proposes that metabolic adaptations hard-wired into primary cancer lesions dictate patterns of distal organ-specific metastatic colonization. We highlight how fatty acid synthase (FASN)–the central enzyme in de novo lipogenesis that synthesize de novo the long-chain saturated fatty acid (FA) palmitate from acetyl-CoA, malonyl-CoA, and NADPH–is an unforeseen cause of metabolic heterogeneity that can promote brain-specific metastasis from primary HER2+ breast tumors [25]. The recognition of endogenous FA synthesis as a novel driver of metastatic tissue tropism, which allows breast cancer cells to adapt, survive, and ‘reproduce’ in the brain, might ultimately lead to improved clinical outcomes for patients with BrM [25,26]. By delineating how the FASN lipogenic signaling enables BrM, we offer a critical review both on the opportunities and the challenges of incorporating next-generation FASN inhibitors into the armamentarium against BrM.