Association of melatonin &amp; MTNR1B variants with type 2 diabetes in Gujarat population

Patel, Roma; Rathwa, Nirali; Palit, Sayantani Pramanik; Ramachandran, A. V.; Begum, Rasheedunnisa

doi:10.1016/j.biopha.2018.04.058

Cited by 29 publications

(10 citation statements)

References 31 publications

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“…Additionally, melatonin injection in lipopolysaccharideinduced endotoxemia markedly improves energy metabolism by enhancing ATP production (13). A similar effect of melatonin is also observed in diabetes, where lower melatonin secretion is independently associated with a higher risk of developing type 2 diabetes (14,15). These findings indicate an interaction between melatonin signaling and metabolic diseases.…”

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confidence: 73%

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

Yin

Han

et al. 2020

mSystems

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Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice. IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.

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confidence: 73%

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

Yin

Han

et al. 2020

mSystems

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“…Our previous reports suggest interleukin 1β (IL1β) 22 , resistin 23 and TNFα 24 to play an important role in the development of obesity, islet dysfunction and decreased insulin secretion. On the contrary, adiponectin 2 , omentin-1 25 , melatonin 26 and vaspin 27 are known to enhance insulin sensitivity. The normal range of total adiponectin in healthy individuals is reported to be 2-20 µg/mL 28 .…”

Section: Discussionmentioning

confidence: 99%

A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes

Palit

Patel

Jadeja

et al. 2020

Sci Rep

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Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (Snps) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ Snps: −11377C/G, +10211T/G, +45T/G and +276G/T for the risk towards type 2 diabetes (T2D) and, (2) genotype-phenotype association of these SNPs with various biochemical parameters in two cohorts. Genomic DNA of diabetic patients and controls from Gujarat and, Jammu and Kashmir (J&K) were genotyped using PCR-RFLP, TaqMan assay and MassArray. transcript levels of ADIPOQ were assessed in visceral adipose tissue samples, and plasma adiponectin levels were estimated by qPCR and ELISA respectively. Results suggest: (i) reduced HMW adiponectin/ total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of −11377C/G with T2D in J&K population. Reduced HMW adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D.Metabolic Syndrome (MS) is the new wave of diseases that has hit the human population in the last few decadesthe Metabolic Syndrome Era. It has become pandemic and with obesity and type 2 diabetes (T2D) clubbed under the MS umbrella, millions of people around the globe have come under its grip. Though obesity and T2D are ubiquitous, there exists a pattern of prevalence based on ethnicity. A recent report has identified demographic transitions, nutrition and lifestyle in the backdrop of genetic predisposition as the chief factors responsible for the rising trend of obesity associated amongst South Asians 1 . Over accumulation of visceral adipose tissue (AT) has been identified as one of the major driving factors towards T2D. Adipose tissue is an important regulator of metabolic homeostasis by virtue of the adipokines (pro-inflammatory and anti-inflammatory) that it secretes. In obese conditions, the fine-tuned balance between the pro-and anti-inflammatory adipokines gets altered leading to various metabolic disorders 2 . These bioactive peptides act locally and distally to calibrate and fine tune various metabolic pathways. Adiponectin is one such calibrator which is abundantly expressed in white adipose tissue 3 . It circulates in three polymorphic forms, low molecular weight (LMW), moderate molecular weight (MMW) and high molecular weight (HMW). Interestingly, the ratio of plasma HMW adiponectin to total adiponectin is more strongly correlated with plasma glucose levels than any of the forms alone 4 . Adiponectin gene (ADIPOQ/ APM1/GBP28) locus, 3q27, has been strongly associated with a variety of metabolic disorders like-impaired glucose tolerance, obesity, dys...

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“…In the context of metabolic syndrome, melatonin secretion levels are low in patients with insulin resistance and impaired glucose tolerance [ 113 ], and mutations in MTNR1B gene are associated with an increased risk of diabetes [ 114 , 115 ]. Moreover, the nuclear melatonin receptor RORα is down-regulated in the diabetic heart, and its deficiency aggravates the diabetic cardiomyopathy and HF [ 36 ].…”

Section: Current Challenges and Perspectives In The Use Of Melatonmentioning

confidence: 99%

Melatonin in Heart Failure: A Promising Therapeutic Strategy?

Nduhirabandi

Maarman

2018

Molecules

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Heart failure is a multifactorial clinical syndrome characterized by the inability of the heart to pump sufficient blood to the body. Despite recent advances in medical management, poor outcomes in patients with heart failure remain very high. This highlights a need for novel paradigms for effective, preventive and curative strategies. Substantial evidence supports the importance of endogenous melatonin in cardiovascular health and the benefits of melatonin supplementation in various cardiac pathologies and cardiometabolic disorders. Melatonin plays a crucial role in major pathological processes associated with heart failure including ischemic injury, oxidative stress, apoptosis, and cardiac remodeling. In this review, available evidence for the role of melatonin in heart failure is discussed. Current challenges and possible limitations of using melatonin in heart failure are also addressed. While few clinical studies have investigated the role of melatonin in the context of heart failure, current findings from experimental studies support the potential use of melatonin as preventive and adjunctive curative therapy in heart failure.

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Association of melatonin & MTNR1B variants with type 2 diabetes in Gujarat population

Cited by 29 publications

References 31 publications

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes

Melatonin in Heart Failure: A Promising Therapeutic Strategy?

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