Increasing the Duration of Light Physical Activity Ameliorates Insulin Resistance Syndrome in Metabolically Healthy Obese Adults

Al-Rashed, Fatema; Alghaith, Abdulwahab; Azim, Rafaat; AlMekhled, Dawood; Thomas, Reeby; Sindhu, Sardar; Ahmad, Rasheed

doi:10.3390/cells9051189

Cited by 11 publications

(10 citation statements)

References 53 publications

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“…This was true in both overweight/obese and the normal weight groups. Physical activity is known to improve insulin sensitivity ( 38 , 39 ) , including in obese individuals ( 40 ) . Furthermore, it lowers blood pressure and improves lipid profile ( 41 , 42 ) .…”

Section: Discussionmentioning

confidence: 99%

Characterisation of body size phenotypes in a middle-aged Maltese population

2021

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Obesity is increasingly recognised as being a heterogeneous disease. Some obese individuals may present a metabolically healthy profile (metabolically healthy obese (MHO)), while some normal weight individuals exhibit an adverse cardiometabolic phenotype (metabolically unhealthy normal weight individuals (MUHNW)). The objectives of the present study were to examine the prevalence and associated characteristics of the different body composition phenotypes within a Maltese cohort. This was a cross-sectional analysis involving 521 individuals aged 41 ± 5 years. The metabolically unhealthy state was defined as the presence of ≥2 metabolic syndrome components (NCEP-ATPIII parameters), while individuals with ≤1 cardiometabolic abnormalities were classified as metabolically healthy. Overall, 70 % of the studied population was overweight or obese and 30⋅7 % had ≥2 cardiometabolic abnormalities. The prevalence of MHO and MUHNW was 10⋅7 and 2⋅1 %, respectively. Individuals with the healthy phenotype were more likely to consume alcohol, participate in regular physical activity and less likely to be smokers. While the MHO phenotype had similar values for waist, hip and neck circumferences, waist–hip ratio and insulin resistance when compared with MUHNW individuals, there was a lower proportion of MHO subjects having a high fasting plasma glucose, hypertriglyceridaemia or low HDL-C when compared with the unhealthy lean individuals. A high prevalence of the metabolically unhealthy phenotype was observed in this relatively young population which may result in significant future cardiovascular disease burden if timely assessment and management of modifiable risk factors are not implemented. Furthermore, the present study suggests that the MHO phenotype is not totally benign as previously thought.

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Section: Discussionmentioning

confidence: 99%

Characterisation of body size phenotypes in a middle-aged Maltese population

2021

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“…Macrophages were cultured and treated as mentioned above, and supernatants were collected after the last 12 h incubation. Secreted IL-1β and MCP-1 proteins were measured in the supernatants using sandwich ELISA, following the manufacturers’ instructions (R&D systems, Minneapolis, MN, USA) [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway

Al-Rashed

Sindhu

Arefanian

et al. 2020

Cells

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Repetitive intermittent hyperglycemia (RIH) is an independent risk factor for complications associated with type-2 diabetes (T2D). Glucose fluctuations commonly occur in T2D patients with poor glycemic control or following intensive therapy. Reducing blood glucose as well as glucose fluctuations is critical to the control of T2D and its macro-/microvascular complications. The interferon regulatory factor (IRF)-5 located downstream of the nutrient sensor toll-like receptor (TLR)-4, is emerging as a key metabolic regulator. It remains unclear how glucose fluctuations may alter the IRF5/TLR4 expression and inflammatory responses in monocytes/macrophages. To investigate this, first, we determined IRF5 gene expression by real-time qRT-PCR in the white adipose tissue samples from 39 T2D and 48 nondiabetic individuals. Next, we cultured THP-1 macrophages in hypo- and hyperglycemic conditions and compared, at the protein and transcription levels, the expressions of IRF5, TLR4, and M1/M2 polarization profile and inflammatory markers against control (normoglycemia). Protein expression was assessed using flow cytometry, ELISA, Western blotting, and/or confocal microscopy. IRF5 silencing was achieved by small interfering RNA (siRNA) transfection. The data show that adipose IRF5 gene expression was higher in T2D than nondiabetic counterparts (p = 0.006), which correlated with glycated hemoglobin (HbA1c) (r = 0.47/p < 0.001), homeostatic model assessment of insulin resistance (HOMA-IR) (r = 0.23/p = 0.03), tumor necrosis factor (TNF)-α (r = 0.56/p < 0.0001), interleukin (IL)-1β (r = 0.40/p = 0.0009), and C-C motif chemokine receptor (CCR)-2 (r = 0.49/p < 0.001) expression. IRF5 expression in macrophages was induced/upregulated (p < 0.05) by hypoglycemia (3 mM/L), persistent hyperglycemia (15 mM/L–25 mM/L), and RIH/glucose fluctuations (3–15 mM/L) as compared to normoglycemia (5 mM/L). RIH/glucose fluctuations also induced M1 polarization and an inflammatory profile (CD11c, IL-1β, TNF-α, IL-6, and monocyte chemoattractant protein (MCP)-1) in macrophages. RIH/glucose fluctuations also drove the expression of matrix metalloproteinase (MMP)-9 (p < 0.001), which is a known marker for cardiovascular complication in T2D patients. Notably, all these changes were counteracted by IRF5 silencing in macrophages. In conclusion, RIH/glucose fluctuations promote the M1 polarization and inflammatory responses in macrophages via the mechanism involving TLR4-IRF5 pathway, which may have significance for metabolic inflammation.

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Section: Crf and Metabolic Healthmentioning

confidence: 99%

“…63 Recent data in MHO individuals also support these findings as both total PA and light PA duration were negatively correlated with inflammatory cytokine levels, while increased light PA was associated with lower insulin resistance and C-peptide levels. 64 In fact, according to a previous systematic review, higher level of PA counteracts the increased CVD risk in MHO, thus investigations of the MHO phenotype should include PA assessments. 65 Bearing in mind the importance of body fat distribution and low-grade systemic inflammation in metabolic health, it is evident that increased engagement in PA and exercise training can provide a pragmatic solution for the prevention of metabolic abnormalities.…”

Section: Crf and Metabolic Healthmentioning

confidence: 99%

Role of physical activity and cardiorespiratory fitness in metabolically healthy obesity: a narrative review

Murlasits

Kupai

Kneffel

2022

BMJ Open Sport Exerc Med

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Obesity has been associated with a multitude of metabolic disorders, often clustering with risk factors of cardiovascular disease and type 2 diabetes mellitus, hypertension, dyslipidaemia. Overall, obesity is a worldwide, growing health concern. However, a subgroup of obese individuals with a low burden of metabolic abnormalities have been identified and described as metabolically healthy obese (MHO). Whether the MHO phenotype is protective against obesity-related metabolic disorders in the long-term is presently unclear, and current research examining the potential transition has yielded inconsistent results. In this current narrative review, we aim to provide insights on the role of physical activity (PA) and cardiorespiratory fitness (CRF) in MHO. Lifestyle factors such as PA and CRF may influence the MHO phenotype. Limited studies have characterised energy expenditure and CRF in MHO and metabolically unhealthy obese. However, higher levels of PA, less sedentary behaviour and higher CRF have been observed in MHO individuals. Considering the multiple benefits of PA, it is high time to advocate this lifestyle change beyond its influence on energy balance in a weight loss programme to improve cardiovascular and metabolic risk factors irrespective of body weight and fat mass changes. Improved CRF via increased PA, especially exercise participation, while avoiding weight gain is not only a realistic goal, but should be the primary intervention for MHO populations to prevent the transition to an abnormal metabolic state.

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Increasing the Duration of Light Physical Activity Ameliorates Insulin Resistance Syndrome in Metabolically Healthy Obese Adults

Cited by 11 publications

References 53 publications

Characterisation of body size phenotypes in a middle-aged Maltese population

Characterisation of body size phenotypes in a middle-aged Maltese population

Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway

Role of physical activity and cardiorespiratory fitness in metabolically healthy obesity: a narrative review

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