Metabolic Alterations in Muscle Associated with Obesity
Emmanuel Opara in NUTRITION and DIABETES, 2005
It has long been known that brown adipose tissue has a high capacity for heat production, because the mitochondria of this tissue contains a protein called uncoupling protein (UCP1), which dissipates the proton gradient through the inner membrane, with the energy being released as heat instead of ATP synthesis. Since obesity is associated with energy imbalance, it was speculated that more uncoupling protein might protect against obesity. Evidence to support this hypothesis was provided by an experiment in which UCP1 was overexpressed in skeletal muscle. The UCP1 overexpressing transgenic mice were resistant to weight gain and obesity when placed on a high-fat diet.66 However, since UCP1 is normally only found in brown adipose tissue, and humans have little or no brown adipose tissue, the significance of UCP1 in human obesity is questionable.
Roles of Daily Diet and Beta-Adrenergic System in the Treatment of Obesity and Diabetes
Nilanjana Maulik in Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
Curcumin is an active compound of turmeric and its antiobesity effect has been demonstrated in experimental studies (Alappat and Awad 2010; Jimenez-Osorio, Monroy et al. 2016). Its role in obesity has been suggested to be related to its effects on mitochondrial biogenesis. In 3T3-L1 and primary white adipocytes, curcumin caused AMPK activation and peroxisome proliferator activated receptor ɣ coactivator 1α (PGC-1α) upregulation. Furthermore, in adipocytes curcumin increased protein expression of carnitin palmitoyltransferase-1 (CPT-1), hormone sensitive lipase (HSL) and phosphorylation of acetyl-coenzyme A carboxylase (ACC), which further led to attenuated lipid accumulation (Lone, Choi et al. 2016). Animal studies confirmed the beneficial effect of curcumin in obesity as browning of the white adipose tissue was stimulated in curcumin fed C57B/6 mice (Wang, Wang et al. 2015). Uncoupling protein 1 (UCP-1) was also upregulated in these mice. These findings suggest that the antiobesity effect of curcumin may be related to mitochondrial biogenesis in white adipose tissue (Lai, Wu et al. 2015).
Mitochondrial Dysfunction and Barth Syndrome
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Recently, researchers have defined a role for CL in the activation of thermogenic adipocytes. Brown adipose tissue (BAT) converts carbohydrate and lipid substrates to thermal energy in response to cold environments. Lynes et al. measured cold-activated lipid landscapes in blood and adipose tissue by MS/MSALL, and among the 1,600 unique lipid species profiled, they identified the CL biosynthetic pathway as coordinately activated in brown and beige fat by cold115. Further, they found CRLS1, the gene encoding CL synthase, to be significantly enriched in cold-induced interscapular BAT as compared with other metabolic tissues, and that loss of CRLS1, and therefore CL, abolished the thermogenic capacity of the adipose tissue116. This suggests that CL is likely to have brown and beige fat-specific functions in thermogenesis. Previous studies have demonstrated that CL binds to the uncoupling protein, UCP1, and assists its proper folding. Therefore, CL may function through the direct activation of the thermogenic effector UCP1117. Additionally, CL also physically interacts with creatine kinase, an enzyme that drives thermogenesis in beige fat118. Together, this suggests that CL is critical for thermogenic mechanisms, adding to the ever growing list of CL functions (Figure 3).
CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population
Published in Psychiatry and Clinical Psychopharmacology, 2019
Selin Kurnaz, Ahmet Bulent Yazici, Ayse Feyda Nursal, Pinar Cetinay Aydin, Ayca Ongel Atar, Nazan Aydin, Zeliha Kincir, Sacide Pehlivan
Catechol-O-methyltransferase (COMT) is an enzyme found all over the mammalian central nervous system which breaks down the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A common G-to-A transition in exon 4 of the COMT gene, causing a valine (val)-to-methionine (met) substitution at the amino acid position 108 or 158 (depending on the splice variant), results in a four-fold reduction in enzyme activity in met homozygotes, whereas heterozygotes manifest intermediate activity [3]. The endocannabinoid system plays a role in susceptibility to substance abuse. There are two well-defined cannabinoid receptors (CNRs), CNR1/CB1 and CNR2/CB2, that mediate endocannabinoid signalling [4]. CNR2 has been classically defined as the peripheral cannabinoid receptor because CNR2 is expressed principally in some peripheral and immune cells [5]. Uncoupling protein 2 (UCP2) is a member of an anion-carrier protein family found in the mitochondrial inner membrane. In the central nervous system, mammalian UCP2 mRNA and protein expression occurs at highest levels in regions that could be described as high-risk for stress [6]. The Interleukin 17 (IL-17 or IL-17A) is a fundamental pro-inflammatory cytokine that is primarily released from T cells and is now believed to be the defining cytokine of a recently discovered new subset of T-helper cells, Th17 [7]. New studies have reported that cells of the central nervous system also express IL-17.
Polyunsaturated fatty acids and endocannabinoids in health and disease
Published in Nutritional Neuroscience, 2018
Hércules Rezende Freitas, Alinny Rosendo Isaac, Renato Malcher-Lopes, Bruno Lourenço Diaz, Isis Hara Trevenzoli, Ricardo Augusto De Melo Reis
The effect of the ECS on brown adipose tissue can be direct or indirect through sympathetic activation. Brown adipocyte function is highly dependent on the sympathetic nervous system (SNS) with activation of beta 3-adrenoceptor signaling (β3AR). Adrenergic signaling results in the activation of thermogenic program and heat production, which is dependent on the activity of uncoupling protein 1 (UCP1), a protein located in the inner membrane of mitochondria. UCP1 is responsible for proton leak from the intermembrane space to the mitochondrial matrix with production of energy in the form of heat instead of ATP. Recent studies have been conducted to better understand the physiology and the pathophysiological aspects of the BAT in metabolic disorders such as obesity, especially because it was demonstrated that brown adipocytes are active in adult humans (reviewed at Labbe et al.215).
Panax ginseng root, not leaf, can enhance thermogenic capacity and mitochondrial function in mice
Published in Pharmaceutical Biology, 2020
Su-hui Wu, Han-bing Li, Gen-Lin Li, Yue-juan Qi, Juan Zhang, Bai-yan Wang
Brown adipose tissue (BAT) is very important because of its capacity to enhance energy expenditure (EE) and regulate the energy balance, which is why it has received strong scientific interest over recent years (Virtanen et al. 2009). It is strongly innervated by sympathetic nervous system and can burn off excess energy by uncoupling the oxidative phosphorylation via uncoupling protein 1 (UCP1) on inner mitochondrial membrane, thus causing the ATP production to decrease and energy to dissipate and be released as heat (Cannon and Nedergaard 2004; Oelkrug et al. 2015). As has been noted, this is one part of the adaptive thermogenesis. Under the cold circumstances, BAT generates most heat to prevent hypothermia (Zhang and Wang 2006, 2007). So, if the body feels cold, BAT thermogenic capacity is stimulated to produce more heat. During this period, the BAT mitochondrial oxidative phosphorylation is enhanced and state 4 respiration may be higher than before when the ADP is used up in an isolated system due to an uncoupling effect. Liver is another organ which can affect the thermogenesis by accelerating the mitochondrial oxidative phosphorylation occur in state 3 (defined as ADP-stimulated respiration) and 4 respiration.
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