Exploiting Common Aspects of Obesity and Alzheimer’s Disease

Tabassum, Sidra; Misrani, Afzal; Yang, Li

doi:10.3389/fnhum.2020.602360

Cited by 27 publications

(21 citation statements)

References 172 publications

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“…These particular features are associated with chronic inflammation, increased oxidative stress, and impairment in insulin signaling and energy metabolism [23,24]. Additionally, due to the potential multifactorial role of obesity in pathological processes seen in AD, obesity could serve as a risk factor for this disease [25]. Of note, patients with T2DM have a 2-fold higher risk of developing AD than healthy subjects [26].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…An increasing amount of data suggests that adipose tissue-associated inflammation is the primary mechanism by which obesity becomes a risk factor for developing cognitive disorders, especially AD [25,84]. The presence of an adiposity-related inflammatory microenvironment leads to the formation of inflammasome complexes that may amplify innate immune response not only locally in adipose tissue but also in the whole organism, making it systemic [85,86].…”

Section: Adiposity-related Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Litwiniuk

Bik

Kalisz

et al. 2021

IJMS

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Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.

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Section: Alzheimer's Diseasementioning

confidence: 99%

Section: Adiposity-related Inflammationmentioning

confidence: 99%

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Litwiniuk

Bik

Kalisz

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The inflammation induced by the dysregulation of peripheral lipid metabolism links obesity and its complications with AD [ 56 , 89 , 136 ]. Researchers have demonstrated that inflammatory challenges in the periphery trigger neuroinflammation [ 87 ], which can then contribute to the pathogenesis of AD in several ways, including interacting with Aβ metabolism [ 88 , 137 – 139 ].…”

Section: Introductionmentioning

confidence: 99%

“…Peripheral IR is associated with dysregulated lipid metabolism, resulting in the overload of FFAs and the activation of cytokines in the periphery. Excessive levels of peripheral cytokines can cross and damage the BBB, leading to neuroinflammation and therefore inducing brain IR [ 89 ]. This mechanism has been supported by several experiments with rodent models that demonstrated that chronic peripheral IR may lead to brain IR as well as brain dysfunction [ 149 , 150 ].…”

Section: Introductionmentioning

confidence: 99%

TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target

Qin

Yang

et al. 2022

Mol Neurodegeneration

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Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane immune receptor that is mainly expressed on microglia in the brain and macrophages in the periphery. Recent studies have identified TREM2 as a risk factor for Alzheimer’s disease (AD). Increasing evidence has shown that TREM2 can affect lipid metabolism both in the central nervous system (CNS) and in the periphery. In the CNS, TREM2 affects the metabolism of cholesterol, myelin, and phospholipids and promotes the transition of microglia into a disease-associated phenotype. In the periphery, TREM2 influences lipid metabolism by regulating the onset and progression of obesity and its complications, such as hypercholesterolemia, atherosclerosis, and nonalcoholic fatty liver disease. All these altered lipid metabolism processes could influence the pathogenesis of AD through several means, including affecting inflammation, insulin resistance, and AD pathologies. Herein, we will discuss a potential pathway that TREM2 mediates lipid metabolism to influence the pathogenesis of AD in both the CNS and periphery. Moreover, we discuss the possibility that TREM2 may be a key factor that links central and peripheral lipid metabolism under disease conditions, including AD. This link may be due to impacts on the integrity of the blood–brain barrier, and we introduce potential pathways by which TREM2 affects the blood–brain barrier. Moreover, we discuss the role of lipids in TREM2-associated treatments for AD. We propose some potential therapies targeting TREM2 and discuss the prospect and limitations of these therapies.

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“…A recent meta-analysis suggested that sarcopenia is associated with cognitive dysfunction [ 4 ]. The correlation between obesity and cognitive dysfunction has been shown in several investigations [ 5 , 6 ]. Exacerbated insulin resistance [ 7 ], energy metabolism dysregulation [ 8 ], and increased oxidative stress and neuroinflammation [ 9 ] have been proposed as potential causal factors.…”

Section: Introductionmentioning

confidence: 99%

Potential Effects of Resistant Exercise on Cognitive and Muscle Functions Mediated by Myokines in Sarcopenic Obese Mice

2022

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Recently, it has been demonstrated that in sarcopenic obesity (SO), physical activity could improve cognitive functions. Moreover, previous studies suggested that muscle contraction could influence cognitive function via myokines. This study investigated the potential effects of resistant exercise on cognitive and muscle functions in SO. SO was induced by a high-fat diet treatment for 8 weeks in 8-month-old male C57BL/6J mice. Then, resistant exercise (ladder climbing) for 8 weeks was performed. Muscle and cognitive function tests and morphological analysis were conducted. The protein levels of myokines were investigated in muscle, plasma, and the hippocampus in sarcopenic obese mice. Muscle and cognitive functions were significantly elevated in the obesity-exercise group (EX) compared to the obesity-control group (OB). Interestingly, muscle function was positively correlated with cognitive function. Abnormal morphological changes in the hippocampus were ameliorated in EX compared to OB, but not in the muscle. Protein levels of cognitive function-related myokines and energy metabolism-related markers in EX were significantly elevated in both muscle and hippocampus compared to those in OB. Interestingly, the protein level of brain-derived neurotrophic factor (BDNF) in EX was simultaneously increased in all tissues including muscle, plasma, and hippocampus compared to that in OB. In conclusion, modulation of muscle-derived cognitive function-related myokines in various pathological conditions via a resistant exercise could be a possible way of relieving muscle and cognitive dysfunction.

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Exploiting Common Aspects of Obesity and Alzheimer’s Disease

Cited by 27 publications

References 172 publications

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target

Potential Effects of Resistant Exercise on Cognitive and Muscle Functions Mediated by Myokines in Sarcopenic Obese Mice

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