Insulin Resistance, Obesity and Lipotoxicity

Yazıcı, Dilek; Sezer, Havva

doi:10.1007/978-3-319-48382-5_12

Cited by 369 publications

(237 citation statements)

References 189 publications

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“…The reduction in lipogenesis observed with systemic dopamine agonist administration was coupled with a substantial increase in the protein turnover rate, and such an action is a major contributor to the resting metabolic rate. If adipose and non‐adipose tissue lipid stores are reduced as a result of energy flux away from lipid accretion and towards protein turnover, the adverse impact of the HFD on both body fat store level and insulin sensitivity (eg, via the facilitation of lipotoxicity) may be expected to be lessened, as observed in the present study. Such systemic dopamine agonist treatment also reduced elevated sympathetic tone, hypertension, hyperleptinaemia, and hepatic inflammatory and gluconeogenic activity, consequently reducing multiple components of insulin resistance syndrome.…”

Section: Discussionmentioning

confidence: 51%

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

Luo

Zhang

Ezrokhi

et al. 2018

J Neuroendocrinology

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Among vertebrate species of the major vertebrate classes in the wild, a seasonal rhythm of whole body fuel metabolism, oscillating from a lean to obese condition, is a common biological phenomenon. This annual cycle is driven in part by annual changes in the circadian dopaminergic signalling at the suprachiasmatic nuclei (SCN), with diminution of circadian peak dopaminergic activity at the SCN facilitating development of the seasonal obese insulin-resistant condition. The present study investigated whether such an ancient circadian dopamine-SCN activity system for expression of the seasonal obese, insulin-resistant phenotype may be operative in animals made obese amd insulin resistant by high-fat feeding and, if so, whether reinstatement of the circadian dopaminergic peak at the SCN would be sufficient to reverse the adverse metabolic impact of the high-fat diet without any alteration of caloric intake. First, we identified the supramammillary nucleus as a novel site providing the majority of dopaminergic neuronal input to the SCN. We further identified dopamine D2 receptors within the peri-SCN region as being functional in mediating SCN responsiveness to local dopamine. In lean, insulin-sensitive rats, the peak in the circadian rhythm of dopamine release at the peri-SCN coincided with the daily peak in SCN electrophysiological responsiveness to local dopamine administration. However, in rats made obese and insulin resistant by high-fat diet (HFD) feeding, these coincident circadian peak activities were both markedly attenuated or abolished. Reinstatement of the circadian peak in dopamine level at the peri-SCN by its appropriate circadian-timed daily microinjection to this area (but not outside this circadian time-interval) abrogated the obese, insulin-resistant condition without altering the consumption of the HFD. These findings suggest that the circadian peak of dopaminergic activity at the peri-SCN/SCN is a key modulator of metabolism and the responsiveness to adverse metabolic consequences of HFD consumption. K E Y W O R D Scircadian, diabetes, dopamine, insulin sensitivity, suprachiasmatic nucleiThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 51%

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

Luo

Zhang

Ezrokhi

et al. 2018

J Neuroendocrinology

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“…Numerous studies indicate that visceral obesity is the main cause of insulin resistance and MS [30]; nevertheless, the causes of reduced insulin sensitivity in the target organs are not exactly known. It is suggested that the common denominator of these metabolic disturbances may be redox imbalance as well as increased oxidative stress [31]. Moreover, despite the proven effectiveness of bariatric surgery, it is unclear whether it improves the redox homeostasis of morbidly obese cases.…”

Section: Discussionmentioning

confidence: 99%

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

Choromańska

Myśliwiec

Łuba

et al. 2020

JCM

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This is the first study to evaluate both the antioxidant barrier, glutathione metabolism, and oxidative damage to proteins and lipids in morbidly obese patients undergoing bariatric treatment. The study included 65 patients with class 3 obesity divided into two subgroups: morbidly obese patients without metabolic syndrome (OB) and obese patients with metabolic syndrome (OB + MS). Blood samples were collected before surgery as well as one, three, six, and twelve months after the bariatric treatment. Superoxide dismutase and reduced glutathione (GSH) were significantly decreased, whereas glutathione reductase and uric acid were enhanced in morbidly obese patients before bariatric surgery as compared to lean control. Moreover, in the OB group, we observed the increase of superoxide dismutase (SOD) and the decrease of uric acid (UA) after the bariatric treatment; however, these changes were not observed in the OB + MS group. The oxidative damage to proteins (advanced glycation end products, AGE; advanced oxidation protein products, AOPP) and lipids (8-isoprostanes, 8-isop; 4-hydroxynoneal) was higher in OB as well as OB + MS patients. We noticed that AGE and AOPP levels diminished after the bariatric treatment, whereas redox status (ratio of GSH to oxidized glutathione) was still reduced in the OB + MS group. Summarizing, morbid obesity is associated with disturbances in the antioxidant barrier and enhanced oxidative damage to proteins and lipids. Although bariatric surgery improves redox homeostasis in obese patients, those with metabolic syndrome show a continuous decrease in the antioxidant status. In patients undergoing bariatric treatment, antioxidant supplementation may be considered.

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“…JNK3 is only expressed in the brain, heart and testis [57,58]. In obese mice, increased lipid toxicity pressure activates JNK, and JNK activation leads to insulin resistance [59]. By comparing the effects of GSPE on lipid deposition in mice fed with a normal diet and high-fat diet, it was found that GSPE decreased the expression of FA synthase, C/EBPα protein and MPARγ peroxidase receptor mRAN, which are the lipid production-related genes, through inhibiting the JNK pathway effectively reduced fat deposition [60][61][62] and showed a dose dependency.…”

Section: Inhibiting the C-jun Aminoterminal Kinase Pathwaymentioning

confidence: 99%

Effects of Grape Seed Proanthocyanidin Extract on Obesity

Liu

Peng

et al. 2020

Obes Facts

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Obesity is a chronic metabolic disease resulting from excessive fat accumulation and/or abnormal distribution caused by multiple factors. As a major component of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes mellitus, hyperlipidemia, hypertension, coronary heart disease, stroke and cancer. Hence, the problem of obesity cannot be ignored, and recent studies have shown that grape seed proanthocyanidin extract (GSPE) has an antiobesity effect. This paper systematically reviews the research progress and potential mechanism of GSPE emphasizing on obesity prevention and treatment.has increased from 105 million in 1975 to 641 million in 2014 [8]. In a nutshell, obesity poses a serious threat to the health of individuals, and more and more evidence shows that obesity is an important risk factor affecting the morbidity and mortality in cardiovascular diseases; also, overweight can increase the mortality of adults suffering from cardiovascular diseases [9]. The body mass index has a linear relationship with the mortality rate of coronary artery disease, stroke and diabetes mellitus [10]. Even modest weight loss can also reduce the risk of these complications [11]. In addition, obesity can lead to gastrointestinal disorders, joint and muscle diseases, respiratory system problems and psychological problems [12,13]. In short, obesity is an increasingly serious global public health problem, which seriously affects the daily life of obese people and increases the risk of mortality.How to prevent and treat obesity has been the focus of attention. Behavioral exercise and drug therapy [14], surgical weight loss [15] and dietary intervention therapy [16] have been the focus of research. But the effect of behavioral exercise on weight loss is slow and obviously unsuitable for obese patients with cardiovascular diseases; every weight loss drug has its own unique risk characteristics, so the doctor needs to fully understand drug contraindications and the differences among obese individuals [17]. More importantly, there is still a lack of long-term experimental studies on whether drug weight loss can cause side effects. Besides, the way of surgical weight loss has been considered controversial for a long time. It can reduce obesity in a short period of time, as 10-30% of patients who undergo gastric bypass surgery lose weight by 40 or 50% [18]. However, current evidence shows that the benefits of surgical weight loss are not universal. A considerable proportion of patients will experience weight rebound and recurrence of diabetes [19]. Although exercise, drugs and surgery can achieve effective weight loss, they have limitations, risks and instability, and are not suitable for all obese patients. In this context, a safe and reliable method of reducing obesity with fewer side effects is urgently required by obese people. Compared with behavior, drugs and surgical treatment, dietary strategies for losing weight or improving obesity-related conditions seem to be more anticipated. The use of plant-d...

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Insulin Resistance, Obesity and Lipotoxicity

Cited by 369 publications

References 189 publications

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

Effects of Grape Seed Proanthocyanidin Extract on Obesity

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