Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control

Vázquez, Gumersindo Fernández; Reíter, Russel J.; Agil, Ahmad

doi:10.1111/jpi.12472

Cited by 95 publications

(76 citation statements)

References 58 publications

(107 reference statements)

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“…This is in keeping with a recent finding showing that dietary therapy with α-lipoic acid induces changes in gene expression in liver and adipose tissues, which ameliorate whole body lipid status in ZDF rats [45]. A recent study showed that the downregulation of UCP-1 mRNA and protein expression in brown adipose tissue in ZDF rats is reversed by six weeks of treatment with the potent antioxidant melatonin [46].Thus, one may suggest that α-lipoic acid exerts its anti-visceral obesity effects through its antioxidant properties, leading to the activation of UCP-1 protein expression at the adipose tissue level in ZDF rats.The beneficial impact of α-lipoic acid to decrease the body weight gain in ZDF rats is consistent with the reduction of NADPH oxidase hyperactivity in adipose tissue [7].…”

Section: Discussionsupporting

confidence: 90%

Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats

et al. 2019

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Evidence suggests that oxidative stress plays a major role in the development of metabolic syndrome. This study aims to investigate whether α-lipoic acid (LA), a potent antioxidant, could exert beneficial outcomes in Zucker diabetic fatty (ZDF) rats. Male 6-week-old ZDF rats and their lean counterparts (ZL) were fed for six weeks with a standard diet or a chow diet supplemented with LA (1 g/kg feed). At 12 weeks of age, ZDF rats exhibited an increase in systolic blood pressure, epididymal fat weight per body weight, hyperglycemia, hyperinsulinemia, insulin resistance (HOMA index), adipocyte hypertrophy and a rise in basal superoxide anion (O2•−) production in gastrocnemius muscle and a downregulation of epididymal uncoupled protein-1 (UCP-1) protein staining. Treatment with LA prevented the development of hypertension, the rise in whole body weight and O2•− production in gastrocnemius muscle, but failed to affect insulin resistance, hyperglycemia and hyperinsulinemia in ZDF rats. LA treatment resulted in a noticeable increase of pancreatic weight and a further adipocyte hypertrophy, along with a decrease in epididymal fat weight per body weight ratio associated with an upregulation of epididymal UCP-1 protein staining in ZDF rats. These findings suggest that LA was efficacious in preventing the development of hypertension, which could be related to its antioxidant properties. The anti-visceral obesity effect of LA appears to be mediated by its antioxidant properties and the induction of UCP-1 protein at the adipose tissue level in ZDF rats. Disorders of glucose metabolism appear, however, to be mediated by other unrelated mechanisms in this model of metabolic syndrome.

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Section: Discussionsupporting

confidence: 90%

Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats

et al. 2019

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“…Mitochondria and its complexes use the energetic substrate provided by HSL . Melatonin‐treated Zucker diabetic and obese rats exposed to cold presented increased mitochondrial mass and complexes I and IV activity . Melatonin role in mitochondrial complexes was also investigated in other tissues, such as liver and brain, in which intraperitoneal melatonin (10 mg kg −1 ) increased mitochondrial complexes I and IV activity in Wistar rats .…”

Section: Discussionmentioning

confidence: 99%

Melatonin multiple effects on brown adipose tissue molecular machinery

Souza

Gallo

Camargo

et al. 2019

Journal of Pineal Research

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Brown adipose tissue (BAT) influences energy balance through nonshivering thermogenesis, and its metabolism daily and seasonal variations are regulated by melatonin through partially known mechanisms. We evaluated the role of melatonin in BAT molecular machinery of male Control, pinealectomized (PINX), and melatonin‐treated pinealectomized (PINX/Mel) adult rats. BAT was collected either every 3 hours over 24 hours or after cold or high‐fat diet (HFD) acute exposure. HFD PINX animals presented decreased Dio2 expression, while HFD PINX/Mel animals showed increased Dio2, Ucp1, and Cidea expression. Cold‐exposed PINX rats showed decreased Dio2 and Lhs expression, and melatonin treatment augmented Adrβ3, Dio2, Ucp1, and Cidea expression. Daily profiles analyses showed altered Dio2, Lhs, Ucp1, Pgc1α, and Cidea gene and UCP1 protein expression in PINX animals, leading to altered rhythmicity under sub‐thermoneutral conditions, which was partially restored by melatonin treatment. The same was observed for mitochondrial complexes I, II, and IV protein expression and enzyme activity. Melatonin absence seems to impair BAT responses to metabolic challenges, and melatonin replacement reverses this effect, with additional increase in the expression of crucial genes, suggesting that melatonin plays an important role in several key points of the thermogenic activation pathway, influencing both the rhythmic profile of the tissue and its ability to respond to metabolic challenges, which is crucial for the organism homeostasis.

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“…These include melatonin and liraglutide . Resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) belongs to a class of compounds called plant polyphenols and is also a phytoalexin produced by plants during environmental stress and infections to help overcome their adverse effects . This inherent ability to provide protection against stress conditions is the main feature that makes resveratrol an attractive candidate for prevention and treatment of human diseases.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

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Summary The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.

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Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control

Cited by 95 publications

References 58 publications

Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats

Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats

Melatonin multiple effects on brown adipose tissue molecular machinery

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

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