Towards a novel marker of insulin resistance in obesity: S100A4 in girls along the puberty. The longitudinal study “PUBMEP”

AbstractIntroduction:Insulin resistance (IR) is the major driver for the development of obesity-associated metabolic and cardiovascular complications. It is well known that IR increase physiologically during puberty; hence, pubertal maturation might favour this metabolic risk in obese children. Recently, a study carried out in adult women with obesity has identified a new adipokine, known as S100A4, strongly associated with IR and inflammation in adipose tissue. On the contrary, little is known about the implication of S100A4 in the development of such metabolic disturbances during the onset and course of pubertal development.Materials and methods:A longitudinal study was conducted on 53 Spanish girls distributed in six experimental conditions according to their obesity and IR status (before (T0) and after (T1) the onset of puberty). Anthropometric and biochemical parameters were evaluated in all samples and time points. Classification of pubertal stage was made according to the Tanner scale. S100A4 protein levels were quantified by ELISA CSB-EL02032HU in plasma samples (Cusabio Biotech, Wuhan, China). The statistical analysis of the results was carried out with the “nlme” package in R v3.4.4, using a mixed-effects linear model with random intercept and slope.Results:At a significance level of alpha = 0.05, a linear mixed-effects model reported a significant association (P = 0.03) between the interaction term “time*experimental group” and S100A4 levels. Post-hoc pairwise comparisons between experimental groups revealed a strong association between a worsening/improvement of the IR status and the increase/decrease of S100A4 levels (yielding significant results for 5 of the 15 comparisons (P = 0.008, P = 0.04, P = 0.02, P = 0.04 and P = 0.02)). Furthermore, a multiple linear regression model reported a positive correlation between the increase in S100A4 levels and the increase in HOMA values during the course of puberty (B = 6.03, SE = 2.66 and P = 0.028).Discussion:The S100A4 protein is strongly associated with the development of IR in girls with childhood obesity and this association is accentuated during pubertal development. Increase in S100A4 levels could be one of the molecular mechanisms by which pubertal maturation favour an increased metabolic risk in children with obesity.

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Resistin 420C/G gene polymorphism on circulating resistin, metabolic risk factors and insulin resistance in adult women

Immunology Letters ◽

10.1016/j.imlet.2014.07.009 ◽

2014 ◽

Vol 162 (2) ◽

pp. 287-291 ◽

Cited By ~ 13

Author(s):

Sandeep Kumar ◽

Vani Gupta ◽

Nidhi Srivastava ◽

Vandana Gupta ◽

Sameeksha Mishra ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Gene Polymorphism ◽

Metabolic Risk Factors ◽

Adult Women ◽

Metabolic Risk

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Supplemental Material for Pubertal Development, Personality, and Substance Use: A 10-Year Longitudinal Study From Childhood to Adolescence

Journal of Abnormal Psychology ◽

10.1037/a0033133.supp ◽

2013 ◽

Keyword(s):

Substance Use ◽

Longitudinal Study ◽

Pubertal Development

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Lilly Lecture: molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene

Diabetes ◽

10.2337/diabetes.41.11.1473 ◽

1992 ◽

Vol 41 (11) ◽

pp. 1473-1490 ◽

Cited By ~ 88

Author(s):

S. I. Taylor

Keyword(s):

Insulin Resistance ◽

Insulin Receptor ◽

Molecular Mechanisms ◽

Receptor Gene ◽

Insulin Receptor Gene

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Molecular mechanisms underlying zinc oxide nanoparticle induced insulin resistance in mice

Nanotoxicology ◽

10.1080/17435390.2019.1663288 ◽

2019 ◽

Vol 14 (1) ◽

pp. 59-76

Author(s):

Hailong Hu ◽

Qian Guo ◽

Xingpei Fan ◽

Xiangjuan Wei ◽

Daqian Yang ◽

...

Keyword(s):

Insulin Resistance ◽

Zinc Oxide ◽

Molecular Mechanisms ◽

Zinc Oxide Nanoparticle ◽

Oxide Nanoparticle

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Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00167 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5372-5381 ◽

Cited By ~ 12

Author(s):

Nigel K Stepto ◽

Alba Moreno-Asso ◽

Luke C McIlvenna ◽

Kirsty A Walters ◽

Raymond J Rodgers

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Polycystic Ovary Syndrome ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Polycystic Ovary ◽

Evidence Synthesis ◽

Basic Research ◽

Future Research ◽

Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

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Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

International Journal of Molecular Sciences ◽

10.3390/ijms22147256 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7256

Author(s):

Vianet Argelia Tello-Flores ◽

Fredy Omar Beltrán-Anaya ◽

Marco Antonio Ramírez-Vargas ◽

Brenda Ely Esteban-Casales ◽

Napoleón Navarro-Tito ◽

...

Keyword(s):

Insulin Resistance ◽

Protein Kinase ◽

Molecular Mechanisms ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Biological Species ◽

Necrosis Factor Alpha ◽

Polypyrimidine Tract Binding Protein ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

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When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22094617 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4617

Author(s):

Styliana Kyriakoudi ◽

Anthi Drousiotou ◽

Petros P. Petrou

Keyword(s):

Insulin Resistance ◽

Mitochondrial Function ◽

Human Disease ◽

Molecular Mechanisms ◽

Mitochondrial Dynamics ◽

Mitochondrial Fusion ◽

Mitochondrial Morphology ◽

Disease Development ◽

Pathological Conditions ◽

Wide Range

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

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Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽

10.3390/cells10051236 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1236

Author(s):

Jesús Burillo ◽

Patricia Marqués ◽

Beatriz Jiménez ◽

Carlos González-Blanco ◽

Manuel Benito ◽

...

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Type 2 Diabetes Mellitus ◽

Insulin Signaling ◽

Molecular Mechanisms ◽

Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

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