Macrophage tumor necrosis factor‐alpha deletion does not protect against obesity‐associated metabolic dysfunction

Al-Adhami, Ahmed; Unger, Christian; Ennis, Shannon L.; Altomare, Diego; Ji, Hao; Hope, Marion C.; Velázquez, Kandy T.; Enos, Reilly T.

doi:10.1096/fj.202100543rr

Cited by 15 publications

(10 citation statements)

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“…Inflammatory processes are an important feature of MetS components; obesity, dyslipidemia, IR, and atherosclerosis are all closely connected with inflammatory processes [90,91].…”

Section: H Pylori-related Mets-induced Inflammation and Arterial Hypertensionmentioning

confidence: 99%

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

et al. 2021

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Arterial hypertension is a risk factor for several pathologies, mainly including cardio-cerebrovascular diseases, which rank as leading causes of morbidity and mortality worldwide. Arterial hypertension also constitutes a fundamental component of the metabolic syndrome. Helicobacter pylori infection is one of the most common types of chronic infection globally and displays a plethora of both gastric and extragastric effects. Among other entities, Helicobacter pylori has been implicated in the pathogenesis of the metabolic syndrome. Within this review, we illustrate the current state-of-the-art evidence, which may link several components of the Helicobacter pylori-related metabolic syndrome, including non-alcoholic fatty liver disease and arterial hypertension. In particular, current knowledge of how Helicobacter pylori exerts its virulence through dietary, inflammatory and metabolic pathways will be discussed. Although there is still no causative link between these entities, the emerging evidence from both basic and clinical research supports the proposal that several components of the Helicobacter pylori infection-related metabolic syndrome present an important risk factor in the development of arterial hypertension. The triad of Helicobacter pylori infection, the metabolic syndrome, and hypertension represents a crucial worldwide health problem on a pandemic scale with high morbidity and mortality, like COVID-19, thereby requiring awareness and appropriate management on a global scale.

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“…Inflammatory processes are an important feature of MetS components; obesity, dyslipidemia, IR, and atherosclerosis are all closely connected with inflammatory processes [90,91].…”

Section: H Pylori-related Mets-induced Inflammation and Arterial Hypertensionmentioning

confidence: 99%

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

et al. 2021

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“…The HFD (4.57 kcal/g) was a purified diet comprised of 47%, 40%, and 13% of total calories from carbohydrate, fat, and protein, respectively, with saturated fat making up 12% of total calories in order to mimic the standard American diet (BioServ, Frenchtown, NJ). Details and previous use of this diet are provided elsewhere 18 – 26 . Mice were housed, 3–5/cage, maintained on a 12:12-h light–dark cycle in a low stress environment (22 °C, 50% humidity, low noise) and given food and water ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…Hepatic and skeletal muscle triglyceride assessments were performed as previously described 28 . For total hepatic lipid assessment, lipids were isolated from the liver utilizing a modified folch extraction method and quantified gravimetrically, as previously described 20 , 26 .…”

Section: Methodsmentioning

confidence: 99%

Congenital adiponectin deficiency mitigates high-fat-diet-induced obesity in gonadally intact male and female, but not in ovariectomized mice

Unger

Al-Adhami

Hope

et al. 2022

Sci Rep

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Epidemiological literature indicates that women are less susceptible to type II diabetes (T2D) than males. The general consensus is that estrogen is protective, whereas its deficiency in post-menopause is associated with adiposity and impaired insulin sensitivity. However, epidemiological data suggests that males are more prone to developing T2D, and at a lower BMI, compared to females during post-menopausal years; suggesting that another factor, other than estrogen, protects females. We proposed to determine if adiponectin (APN) serves as this protective factor. An initial experiment was performed in which gonadally intact male and female mice were fed either a purified low-fat diet (LFD) or high-fat diet (HFD) (40% kcals from fat) for 16 weeks. An additional group of HFD ovariectomy (OVX) mice were included to assess estrogen deficiency’s impact on obesity. Body composition, adipose tissue inflammation, ectopic lipid accumulation as well as glucose metabolism and insulin resistance were assessed. In corroboration with previous data, estrogen deficiency (OVX) exacerbated HFD-induced obesity in female mice. However, despite a higher body fat percentage and a similar degree of hepatic and skeletal muscle lipid accumulation, female OVX HFD-fed mice exhibited enhanced insulin sensitivity relative to HFD-fed males. Therefore, a subsequent HFD experiment was performed utilizing male and female (both gonadally intact and OVX) APN deficient mice (APN−/−) and wildtype littermates to determine if APN is the factor which protects OVX females from the similar degree of metabolic dysfunction as males in the setting of obesity. Indirect calorimetry was used to determine observed phenotype differences. APN deficiency limited adiposity and mitigated HFD-induced insulin resistance and adipose tissue inflammation in gonadally intact male and female, but not in OVX mice. Using indirect calorimetry, we uncovered that slight, but non-statistically significant differences in food intake and energy expenditure leading to a net difference in energy balance likely explain the reduced body weight exhibited by male APN-deficient mice. In conclusion, congenital APN deficiency is protective against obesity development in gonadally intact mice, however, in the setting of estrogen deficiency (OVX) this is not true. These findings suggest that gonadal status dictates the protective effects of congenital APN deficiency in the setting of HFD-induced obesity.

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“…Его влияние на жировой обмен -сложное и многообразное, а дисфункция может способствовать как снижению массы тела, так и развитию ожирения. Так, усиление липогенеза реализуется через следующие процессы: резистентность к инсулину, т. е. создается гиперинсулинемия [37]; стимуляция синтеза жира [38][39][40]; стимуляция секреции ИЛ-6, вызывающего инсулинорезистентность и синтез жира [37]; усиление секреции адипокинов, тормозящих липолиз: лептина, PAI-1 [37]; торможение продукции адипонектина, снижающего инсулинорезистентность и воспаление в жировой ткани, подавляющего выброс глюкозы печенью [37]; снижение термогенеза, осуществляемого адипоцитами, особенно коричневыми [41]; ограничение образования катехоламинов в жировых отложениях и делает жир стабильным [42]; полифагия вследствие инсулинорезистентности [38][39][40].…”

Section: роль фно-α в ожирении и патогенезе сахарного диабета 2 типа ...unclassified

“…Стимуляция липолиза опосредована следующими факторами: хроническое воспаление в жировой ткани, осложнения ожирения, полиморбидность [43]; нарушение углеводного обмена (СД2 часто сопровождается снижением массы тела) [44]; частичный апоптоз жировых клеток [41]; увеличение образования бурого жира, перевод белых адипоцитов в бурые, что стимулирует термогенез и расход энергии (уменьшение запасов жира) [42]; частичное ингибирование действия инсулина на синтез жира [41]; антиадипогенное действие: торможение образования жировой ткани при ожирении («ожирение не бесконечно») [41]; уменьшение пула преадипоцитов и замедление их созревания [42].…”

Section: роль фно-α в ожирении и патогенезе сахарного диабета 2 типа ...unclassified

Tumor necrosis factor α and its role in pathologies

Tereshchenko¹,

Kayushev²

2022

Russian Medical Inquiry

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Over the past years, the views on the role played by tumor necrosis factor α (TNF-α) in the body have changed. The aim of this review is to provide updates on TNF-α functions in various pathological conditions. While working on the review, the authors made search and analysis of full-text reviews and original articles in foreign (English) and Russian languages using such databases as eLIBRARY.RU, Google Scholar, Web of Science, Scopus and PubMed, mostly from 2018–2022. A priority was given to the original publications. TNF-α is a multifunctional pro-inflammatory cytokine which stimulates the production of other cytokines, chemokines, and interferon γ. Also, it is involved in the inflammatory processes during viral, bacterial, and autoimmune diseases. Its hypersecretion affects lipid, fat, and carbohydrate metabolism; promotes atherogenesis; leads to the development of arterial hypertension, type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease; contributes to osteolysis; induces apoptosis of tumor cells in some types of cancer and stimulates metastatic spread and progression in other types. So far, the use of TNF-α inhibitors and the suppression of expression of TNF-α and its receptors has caused disappointment: approx. in 40–50% of cases the inhibition aggravated pathological conditions. The investigation of the cytokine activity is still going on. KEYWORDS: TNF-α, cytokines, inflammation, atherosclerosis, oncogenesis, obesity, diabetes mellitus, adipokines. FOR CITATION: Tereshchenko I.V., Kayushev P.E. Tumor necrosis factor α and its role in pathologies. Russian Medical Inquiry. 2022;6(9):523– 527 (in Russ.). DOI: 10.32364/2587-6821-2022-6-9-523-527.

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Macrophage tumor necrosis factor‐alpha deletion does not protect against obesity‐associated metabolic dysfunction

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 15 publications

References 55 publications

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

Congenital adiponectin deficiency mitigates high-fat-diet-induced obesity in gonadally intact male and female, but not in ovariectomized mice

Tumor necrosis factor α and its role in pathologies

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