Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Апрель 21, 2023

The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic environmental features in their pathogenesis, amplifies the impact susceptibility factors on DM. ectopic expansion adipose tissue excessive accumulation certain nutrients metabolites sabotage metabolic balance via insulin resistance, dysfunctional autophagy, microbiome-gut-brain axis, further exacerbating dysregulation immunometabolism through low-grade systemic inflammation, leading to an accelerated loss functional β-cells gradual elevation blood glucose. Given these intricate connections, most available treatments type 2 DM (T2DM) have a mutual effect each other. For example, anti-obesity drugs can be anti-diabetic some extent, medicines, contrast, shown increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both T2DM. Besides guaranteeing availability accessibility all diagnostic therapeutic tools, clinical experimental investigations pathogenesis two diseases warranted improve efficacy safety newly developed treatments.

Язык: Английский

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Mechanisms of insulin resistance related to white, beige, and brown adipocytes

Molecular Metabolism, Год журнала: 2020, Номер 34, С. 27 - 42

Опубликована: Янв. 7, 2020

The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses the molecular cellular disruptions that contribute to syndrome. However, significant uncertainty remains mechanisms its initiation long-term maintenance. To simplify resistance analysis, review focuses unifying concept adipose tissue a central regulator systemic homeostasis by controlling liver skeletal muscle metabolism. Key aspects function related reviewed are: 1) modes which specific tissues control hepatic output disposal, 2) recently acquired understanding underlying these regulation, 3) steps pathways adversely affected obesity cause resistance. Adipocyte heterogeneity required mediate multiple tolerance. White adipocytes specialize sequestering triglycerides away from liver, muscle, limit toxicity. In contrast, brown/beige are very active directly taking up response β adrenergic signaling enhancing energy expenditure. Nonetheless, white, beige, brown all share common feature secreting factors possibly exosomes act distant homeostasis. Obesity exerts deleterious effects each adipocyte functions

Язык: Английский

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Diet-induced obesity in animal models: points to consider and influence on metabolic markers

Diabetology & Metabolic Syndrome, Год журнала: 2021, Номер 13(1)

Опубликована: Март 18, 2021

Overweight and obesity are a worldwide public health problem. Obesity prevalence has increased considerably, which indicates the need for more studies to better understand these diseases related complications. Diet induced-obesity (DIO) animal models can reproduce human overweight obesity, there many protocols used lead excess fat deposition. So, purpose of this review was identify key points induction through diet, as well identifying necessary endpoints be achieved when inducing gain. For this, we reviewed literature in last 6 years, looking original articles that aimed induce diet. All evaluated should have control group, order verify results found, had worked with Sprague-Dawley Wistar rats, or C57BL-/-6 mice strain. Articles induced by other methods, such genetic manipulation, surgery, drugs were excluded, since our main objective humans, cell culture, non-rodent animals, articles, did not book chapters also excluded. Body weight gain, determinants inflammation, hormonal concentration, blood glycemia, lipid profile, liver health, must together determination development obesity. In addition, select best model each circumstance, it considered breed sex respond differently diet-induced The composition diet calorie overconsumption relevant Finally, is important non-obese group included experimental design.

Язык: Английский

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The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

Cell Metabolism, Год журнала: 2021, Номер 33(3), С. 565 - 580.e7

Опубликована: Март 1, 2021

Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment obesity. However, pharmacologic engagement this process has proven difficult. Using Connectivity Map (CMap) approach, we identified phytochemical hyperforin (HPF) an anti-obesity agent. We found that HPF efficiently promoted by stimulating AMPK and PGC-1α via Ucp1-dependent pathway. LiP-SMap (limited proteolysis-mass spectrometry) combined with microscale thermophoresis assay molecular docking analysis, confirmed dihydrolipoamide S-acetyltransferase (Dlat) direct target HPF. Ablation Dlat significantly attenuated HPF-mediated browning both vitro vivo. Furthermore, genome-wide association study analysis indicated variation DLAT associated obesity humans. These findings suggest lead compound pursuit pharmacological approach to promote energy expenditure

Язык: Английский

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

Genes & Diseases, Год журнала: 2023, Номер 11(3), С. 101026 - 101026

Опубликована: Июль 22, 2023

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. proteins are secreted, lipid-modified molecules that activate the canonical (β-catenin dependent) non-canonical independent) pathways. Cellular behaviors such as proliferation, differentiation, maturation, proper body-axis specification carried out by pathway, which is best characterized of known paths. has emerged an important factor stem cell biology to affect self-renewal cells various tissues. This includes but not limited embryonic, hematopoietic, mesenchymal, gut, neural, epidermal cells. also been implicated tumor exhibit cell-like properties. crucial for bone formation presents potential target therapeutics disorders. Not surprisingly, aberrant associated with wide variety diseases, including cancer. Mutations members cancer can lead unchecked epithelial-mesenchymal transition, metastasis. Altogether, advances understanding dysregulated disease have paved way novel components pathway. Beginning brief overview mechanisms Wnt, this review aims summarize current knowledge cells, aberrations targeting preclinical clinical studies.

Язык: Английский

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cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 9, 2024

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.

Язык: Английский

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Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

Redox Biology, Год журнала: 2017, Номер 12, С. 806 - 813

Опубликована: Апрель 14, 2017

Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal external stimuli, depending on the developmental stage activity of organism. The most common functional subunits adipose tissue, white brown adipocytes, regulate respond endocrine processes, which then determine metabolic rate as well functions. While molecular aspects biology have become clearer in recent past, much less known about sex-specific differences regulation deposition specific role so-called pink adipocytes during lactation females. This review summarises current understanding dynamics with focus energy metabolism functions, focussing mammalian model organisms human-derived data. In females, trans-differentiate pregnancy from subcutaneous are responsible for milk-secretion mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments many disorders.

Язык: Английский

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Dietary polyphenols and their roles in fat browning

The Journal of Nutritional Biochemistry, Год журнала: 2018, Номер 64, С. 1 - 12

Опубликована: Окт. 13, 2018

Язык: Английский

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Cold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity

Biology, Год журнала: 2019, Номер 8(1), С. 9 - 9

Опубликована: Фев. 12, 2019

The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that involved energy expenditure and represents an attractive target to combat both type 2 diabetes. Cold exposure exercise training are two stimuli have been investigated with respect BAT activation, metabolism, contribution of metabolic health. These great interest because they disparate converging effects on activation metabolism. effective mechanism stimulate activity increase glucose lipid uptake through mitochondrial uncoupling, resulting benefits including elevated increased insulin sensitivity. Exercise therapeutic tool marked systemic metabolism affects tissues, BAT. Compared cold exposure, studies focused display conflicting results; majority rodents humans demonstrate reduction reduced storage. In addition investigations utilization, recent structural lipids secreted factors released from BAT, termed batokines. induce opposite responses terms lipids, but important overlap exists between this review, we will discuss similarities differences relation their its relevance for prevention development

Язык: Английский

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The Immune Landscape of Visceral Adipose Tissue During Obesity and Aging

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Май 15, 2020

Obesity and aging represent major health burdens to the global adult population. Both conditions promote development of associated metabolic diseases such as insulin resistance. The visceral adipose tissue (VAT) is a site that becomes dysfunctional during obesity aging, plays significant role their pathophysiology. changes in obese VAT are now recognized be partly driven by chronic local inflammatory state, characterized immune cells typically adopt an phenotype disease. Here, we summarize current knowledge on cell landscape lean, obese, aged conditions, highlighting similarities differences. We also briefly discuss possible linked mechanisms fuel obesity- age-associated dysfunction.

Язык: Английский

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