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Article: Novel Dual Incretin Receptor Agonists in the Spectrum of Metabolic Diseases with a Focus on Tirzepatide: Real Game-Changers or Great Expectations? A Narrative Review.

Liarakos, Alexandros Leonidas / Koliaki, Chrysi

2023 Volume 11, Issue 7

Abstract: The prevalence of metabolic diseases including type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD) increases globally. This highlights an unmet need for identifying optimal therapies for the management of these conditions. ... ...

Abstract	The prevalence of metabolic diseases including type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD) increases globally. This highlights an unmet need for identifying optimal therapies for the management of these conditions. Tirzepatide is a novel dual incretin receptor agonist (twincretin) that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. The aim of this narrative review was to examine the impact of novel twincretins, focusing on tirzepatide, on the management of a wide spectrum of metabolic diseases. Data from preclinical and clinical trials have shown that twincretins significantly reduce blood glucose levels in T2D, and tirzepatide is the first agent of this class that has been approved for the management of T2D. Additionally, the beneficial impact of tirzepatide on weight reduction has been corroborated in several studies, showing that this agent can achieve substantial and sustained weight loss in obese patients with or without T2D. Data also suggest that tirzepatide could be a promising drug for hepatic steatosis reduction in individuals with NAFLD. The remarkable effects of tirzepatide on glycaemic control, weight loss and liver-related outcomes have posed new research questions that are likely to lead to further advancements in the treatment of T2D, obesity and related metabolic disorders.
Language	English
Publishing date	2023-07-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11071875
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Correction to: Update on the Obesity Epidemic: After the Sudden Rise, Is the Upward Trajectory Beginning to Flatten?

Koliaki, Chrysi / Dalamaga, Maria / Liatis, Stavros

Current obesity reports

2023 Volume 12, Issue 4, Page(s) 528

Language	English
Publishing date	2023-10-14
Publishing country	United States
Document type	Published Erratum
ISSN	2162-4968
ISSN (online)	2162-4968
DOI	10.1007/s13679-023-00533-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence.

Koliaki, Chrysi / Katsilambros, Nicholas

International journal of molecular sciences

2022 Volume 23, Issue 6

Abstract: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell ... ...

Abstract	Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship and delineate its therapeutic implications in metabolic disease.
MeSH term(s)	Animals ; Apoptosis ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2/drug therapy ; Humans ; Ligands ; Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics ; TNF-Related Apoptosis-Inducing Ligand/metabolism ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Ligands ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-03-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23063225
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Article ; Online: Update on the Obesity Epidemic: After the Sudden Rise, Is the Upward Trajectory Beginning to Flatten?

Koliaki, Chrysi / Dalamaga, Maria / Liatis, Stavros

Current obesity reports

2023 Volume 12, Issue 4, Page(s) 514–527

Abstract: Purpose of review: To provide an update on current obesity prevalence trends and summarize the available evidence suggesting a possible plateau or stabilization in obesity rates after the previous sudden global rise.: Recent findings: The escalating ... ...

Abstract	Purpose of review: To provide an update on current obesity prevalence trends and summarize the available evidence suggesting a possible plateau or stabilization in obesity rates after the previous sudden global rise. Recent findings: The escalating global obesity epidemic represents one of the most serious public health challenges. There have been some indications that in high-income populations, the rate of obesity increase in adults has been stabilized after the decade 2000-2010, suggesting a possible plateau. Current evidence also suggests that obesity rates have been stabilized in children and adolescents of most economically advanced countries since 2000, which is possibly related to healthier dietary habits and increased levels of physical activity. On the other hand, there is a steady uninterrupted rise in low-income nations, and the universal trend is obesity escalation rather than slowdown, mainly driven by sharp increases in the obesity prevalence of low-income populations. Furthermore, an increasing number of high- and middle-income countries are currently experiencing an epidemic of severe obesity. In high-income populations, severe obesity is expected to double its prevalence from 10 to 20% between 2020 and 2035, posing an enormous threat for healthcare systems. Even if transiently stabilized, the obesity prevalence remains globally at unacceptably high levels, and there is no guarantee that the current stability (if any) will be maintained for long. In this review, we explore the underlying drivers of the global obesity epidemic; we provide possible explanations for the reported slowdown of the obesity rates in some countries; and we overall take a critical perspective on the obesity plateau hypothesis, emphasizing the urgent need for immediate effective actions at population and regional level in order to halt the alarming obesity escalation and its serious health risks.
MeSH term(s)	Child ; Adult ; Adolescent ; Humans ; Obesity, Morbid ; Obesity/epidemiology ; Diet ; Prevalence ; Socioeconomic Factors ; Overweight/epidemiology
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2162-4968
ISSN (online)	2162-4968
DOI	10.1007/s13679-023-00527-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus

Chrysi Koliaki / Nicholas Katsilambros

International Journal of Molecular Sciences, Vol 23, Iss 3225, p

An Update of Experimental and Clinical Evidence

2022 Volume 3225

Abstract	Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship ...
Keywords	tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) ; TRAIL receptors ; type 1 diabetes mellitus (T1DM) ; type 2 diabetes mellitus (T2DM) ; obesity ; insulin resistance ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Non-Classical Aspects of Obesity Pathogenesis and Their Relative Clinical Importance for Obesity Treatment.

Samakidou, Georgia E / Koliaki, Chrysi C / Liberopoulos, Evangelos N / Katsilambros, Nikolaos L

Healthcare (Basel, Switzerland)

2023 Volume 11, Issue 9

Abstract: Obesity is a chronic disease and a major public health problem due to its association with non-communicable diseases and all-cause mortality. An increased energy intake and decreased physical activity have been long recognized as the classical parameters ...

Abstract	Obesity is a chronic disease and a major public health problem due to its association with non-communicable diseases and all-cause mortality. An increased energy intake and decreased physical activity have been long recognized as the classical parameters that contribute to the development of obesity. However, several other, non-classical factors have also been associated with obesity through various complex mechanisms. Some of them are diet related, such as diet quality, dietary habits and speed of eating. Other factors are non-dietary, such as endocrine-disrupting chemicals, sleep quality and quantity, psychotropic medications and light at night. The scope of the present narrative review is to address these non-classical factors that are implicated in the pathogenesis of obesity, to clarify their potential role in the management of obesity and, where possible, to provide some practical clinical recommendations.
Language	English
Publishing date	2023-05-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare11091310
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Article: Intermittent Energy Restriction, Weight Loss and Cardiometabolic Risk: A Critical Appraisal of Evidence in Humans.

Katsarou, Alexia L / Katsilambros, Nicholas L / Koliaki, Chrysi C

Healthcare (Basel, Switzerland)

2021 Volume 9, Issue 5

Abstract: Dietary patterns with intermittent energy restriction (IER) have been proposed as an attractive alternative to continuous energy restriction (CER) for the management of obesity and its associated comorbidities. The most widely studied regimens of IER ... ...

Abstract	Dietary patterns with intermittent energy restriction (IER) have been proposed as an attractive alternative to continuous energy restriction (CER) for the management of obesity and its associated comorbidities. The most widely studied regimens of IER comprise energy restriction on two days per week (5:2), alternate-day energy restriction by 60-70% (ADF), and timely restriction of energy intake during a specific time window within the day (TRF; time-restricted feeding). Although there is some evidence to suggest that IER can exert beneficial effects on human cardiometabolic health, yet is apparently not superior compared to CER, there are still some critical issues/questions that warrant further investigation: (i) high-quality robust scientific evidence regarding the long-term effects of IER (safety, efficacy, compliance) is limited since the vast majority of intervention studies had a duration of less than 6 months; (ii) whether the positive effects of IER are independent of or actually mediated by weight loss remains elusive; (iii) it remains unknown whether IER protocols are a safe recommendation for the general population; (iv) data concerning the impact of IER on ectopic fat stores, fat-free mass, insulin resistance and metabolic flexibility are inconclusive; (v) the cost-effectiveness of IER dietary regimens has not been adequately addressed; (vi) direct head-to-head studies comparing different IER patterns with variable macronutrient composition in terms of safety and efficacy are scarce; and (vii) evidence is limited with regard to the efficacy of IER in specific populations, including males, the elderly and patients with morbid obesity and diabetes mellitus. Until more solid evidence is available, individualization and critical perspective are definitely warranted to determine which patients might benefit the most from an IER intervention, depending on their personality traits and most importantly comorbid health conditions.
Language	English
Publishing date	2021-04-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare9050495
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Article ; Online: Important Considerations for the Treatment of Patients with Diabetes Mellitus and Heart Failure from a Diabetologist's Perspective: Lessons Learned from Cardiovascular Outcome Trials.

Koliaki, Chrysi / Katsilambros, Nicholas

International journal of environmental research and public health

2019 Volume 17, Issue 1

Abstract: Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for ... ...

Abstract	Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for patients with T2DM. Treatment of T2DM in patients with HF can be challenging, considering that these patients are usually elderly, frail and have extensive comorbidities, most importantly chronic kidney disease. The complexity of medical regimens, the high risk clinical characteristics of patients and the potential of HF therapies to interfere with glucose metabolism, and conversely the emerging potential of some antidiabetic agents to modulate HF outcomes, are only some of the challenges that need to be addressed in the framework of a team-based personalized approach. The presence of established HF or the high risk of developing HF in the future has influenced recent guideline recommendations and can guide therapeutic decision making. Metformin remains first-line treatment for overweight T2DM patients at moderate cardiovascular risk. Although not contraindicated, metformin is no longer considered as first-line therapy for patients with established HF or at risk for HF, since there is robust scientific evidence that treatment with other glucose-lowering agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) should be prioritized in this population due to their strong and remarkably consistent beneficial effects on HF outcomes.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Anticoagulants/therapeutic use ; Attitude of Health Personnel ; Comorbidity ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Heart Failure/drug therapy ; Heart Failure/epidemiology ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Middle Aged ; Physicians/psychology ; Risk Factors
Chemical Substances	Anticoagulants ; Hypoglycemic Agents
Language	English
Publishing date	2019-12-24
Publishing country	Switzerland
Document type	Editorial
ISSN	1660-4601
ISSN (online)	1660-4601
DOI	10.3390/ijerph17010155
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Article ; Online: Comment on: Adiponectin gene variant RS rs266729: Relation to lipid profile changes and circulating adiponectin after bariatric surgery.

Koliaki, Chrysi / Kokkinos, Alexander

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

2018 Volume 14, Issue 9, Page(s) 1408–1410

MeSH term(s)	Adiponectin/genetics ; Bariatric Surgery ; Humans ; Lipids ; Obesity, Morbid ; Polymorphism, Single Nucleotide
Chemical Substances	Adiponectin ; Lipids
Language	English
Publishing date	2018-07-01
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2274243-8
ISSN	1878-7533 ; 1550-7289
ISSN (online)	1878-7533
ISSN	1550-7289
DOI	10.1016/j.soard.2018.06.025
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Article ; Online: The Role of Mitochondrial Adaptation and Metabolic Flexibility in the Pathophysiology of Obesity and Insulin Resistance: an Updated Overview.

Tsilingiris, Dimitrios / Tzeravini, Evangelia / Koliaki, Chrysi / Dalamaga, Maria / Kokkinos, Alexander

Current obesity reports

2021 Volume 10, Issue 3, Page(s) 191–213

Abstract: Purpose of review: The term "metabolic flexibility" denotes the dynamic responses of the cellular oxidative machinery in order to adapt to changes in energy substrate availability. A progressive loss of this adaptive capacity has been implicated in the ... ...

Abstract	Purpose of review: The term "metabolic flexibility" denotes the dynamic responses of the cellular oxidative machinery in order to adapt to changes in energy substrate availability. A progressive loss of this adaptive capacity has been implicated in the development of obesity-related comorbidities. Mitochondria are dynamic intracellular organelles which play a fundamental role in energy metabolism, and the mitochondrial adaptation to environmental challenges may be viewed as the functional component of metabolic flexibility. Herein, we attempt to comprehensively review the available evidence regarding the role of mitochondrial adaptation and metabolic flexibility in the pathogenesis of obesity and related morbidities, namely insulin resistance states and non-alcoholic fatty liver disease (NAFLD). Recent findings: Overall, there is a concrete body of evidence to support the presence of impaired mitochondrial adaptation as a principal component of systemic metabolic inflexibility in conditions related to obesity. There are still many unresolved questions regarding the relationship between the gradual loss of mitochondrial adaptability and the progression of obesity-related complications, such as causality issues, the timely appearance and reversibility of the described disturbances, and the generalizability of the findings to the mitochondrial content of every affected tissue or organ. The evidence regarding the causality between the observed associations remains inconclusive, although most of the available data points towards a bidirectional, potentially mutually amplifying relationship. The spectrum of NAFLD is of particular interest, since functional and pathological changes in the course of its development closely mirror the progression of dysmetabolism, if not constituting a dynamic component of the latter.
MeSH term(s)	Energy Metabolism ; Humans ; Insulin Resistance ; Mitochondria/metabolism ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/metabolism
Language	English
Publishing date	2021-04-10
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2162-4968
ISSN (online)	2162-4968
DOI	10.1007/s13679-021-00434-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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