The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions

Pereira, Renata O.; McFarlane, Samy I.

doi:10.15344/2456-8007/2019/136

Cited by 9 publications

(9 citation statements)

References 60 publications

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“…However, it is expected that other, stillunknown factors, could play important roles in this scenario. Recent studies have suggested that the activity of the brown adipose tissue (BAT) could be related to cardiovascular conditions (4)(5)(6)(7)(8). A retrospective study evaluating more than 52,000 patients submitted to 18 F-fluorodeoxyglucose positron emission tomography-computed tomography scans ( 18 F-FDG PET/CT) revealed that BAT glucose uptake was inversely correlated with cardiovascular disease, which was independent of diabetes, hypertension, and dyslipidemia (7).…”

Section: Introductionmentioning

confidence: 99%

Brown fat triglyceride content is associated with cardiovascular risk markers in adults from a tropical region

et al. 2022

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Brown adipose tissue (BAT) is regarded as an interesting potential target for the treatment of obesity, diabetes, and cardiovascular diseases, and the detailed characterization of its structural and functional phenotype could enable an advance in these fields. Most studies evaluating BAT structure and function were performed in temperate climate regions, and we are yet to know how these findings apply to the 40% of the world’s population living in tropical areas. Here, we used 18F-fluorodeoxyglucose positron emission tomography – magnetic resonance imaging to evaluate BAT in 45 lean, overweight, and obese volunteers living in a tropical area in Southeast Brazil. We aimed at investigating the associations between BAT activity, volume, metabolic activity, and BAT content of triglycerides with adiposity and cardiovascular risk markers in a sample of adults living in a tropical area and we showed that BAT glucose uptake is not correlated with leanness; instead, BAT triglyceride content is correlated with visceral adiposity and markers of cardiovascular risk. This study expands knowledge regarding the structure and function of BAT in people living in tropical areas. In addition, we provide evidence that BAT triglyceride content could be an interesting marker of cardiovascular risk.

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Section: Introductionmentioning

confidence: 99%

Brown fat triglyceride content is associated with cardiovascular risk markers in adults from a tropical region

et al. 2022

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“…We have previously shown that OPA1 BKO mice have reduced body mass, increased resting metabolic rates, and are resistant to DIO ( Pereira and McFarlane, 2019 ). To further characterize their metabolic phenotype, we analyzed indirect calorimetry data collected in 12-week-old male mice while housed under thermoneutral conditions and after 12 wk of high-fat feeding.…”

Section: Resultsmentioning

confidence: 99%

“…A subset of OPA1 BKO mice exemplifying this drastic abrogation of DIO ( Figure 1J ) was utilized for analysis of indirect calorimetry. Different than in our previously published study ( Pereira and McFarlane, 2019 ), here we analyzed only mice fed high-fat diet (HFD), instead of simultaneously analyzing both HFD and control groups. Moreover, rather than representing the overall averaged data, we plotted the averaged data for the last 48 hr of data collection for each cycle of the day (light and dark).…”

Section: Resultsmentioning

confidence: 99%

GDF15 is required for cold-induced thermogenesis and contributes to improved systemic metabolic health following loss of OPA1 in brown adipocytes

Jena,

García-Peña,

Weatherford

et al. 2023

eLife

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We previously reported that mice lacking the protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) display induction of the activating transcription factor 4 (ATF4), which promotes fibroblast growth factor 21 (FGF21) secretion as a batokine. FGF21 increases metabolic rates under baseline conditions but is dispensable for the resistance to diet-induced obesity (DIO) reported in OPA1 BKO mice (Pereira et al., 2021). To determine alternative mediators of this phenotype, we performed transcriptome analysis, which revealed increased levels of growth differentiation factor 15 (GDF15), along with increased protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) levels in BAT. To investigate whether ATF4 induction was mediated by PERK and evaluate the contribution of GDF15 to the resistance to DIO, we selectively deleted PERK or GDF15 in OPA1 BKO mice. Mice with reduced OPA1 and PERK levels in BAT had preserved ISR activation. Importantly, simultaneous deletion of OPA1 and GDF15 partially reversed the resistance to DIO and abrogated the improvements in glucose tolerance. Furthermore, GDF15 was required to improve cold-induced thermogenesis in OPA1 BKO mice. Taken together, our data indicate that PERK is dispensable to induce the ISR, but GDF15 contributes to the resistance to DIO, and is required for glucose homeostasis and thermoregulation in OPA1 BKO mice by increasing energy expenditure.

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“… 13 , 30 It also has cardioprotective properties and beneficial effects on metabolic risk factors. 14 , 31 …”

Section: Discussionmentioning

confidence: 99%

Implications of the Serum Concentrations of Neuregulin-4 (Nrg4) in Patients with Coronary Artery Disease: A Case-Control Study

Taheri,

Hosseinzadeh-Attar,

Alipoor

et al. 2023

JTHC

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Background: Neuregulin-4 (Nrg4), a novel brown fat-enriched factor, has been reported to play a crucial role in developing metabolic disorders. The current case-control study aimed to investigate the association between serum Nrg4 and coronary artery disease (CAD). Methods: This study enrolled 43 patients with CAD and 43 subjects with normal coronary arteries diagnosed by coronary angiography. Anthropometric and biochemical parameters were measured and recorded. The serum Nrg4 level was determined using the enzyme-linked immunosorbent assay. The relationships between circulating Nrg4 and CAD and other clinical parameters were analyzed. A receiver operating characteristic analysis was applied to assess the utility of Nrg4 in identifying CAD. Results: The study population comprised 86 patients, including 64 men (74.4%), at a mean age of 57.83±6.01 years. Patients with CAD had significantly lower serum Nrg4 than the control group (P<0.001). The serum Nrg4 level was negatively correlated with anthropometric variables, including the body mass index, waist circumference, and the waist-to-hip ratio, fasting blood glucose, and the triglyceride-glucose index (P<0.05). In multivariable-adjusted regression analysis, the odds of CAD decreased by 46% per 1 SD elevation in the serum Nrg4 level (OR, 0.54; 95% CI, 0.40 to 0.73; P<0.001) after controlling for potential confounders. Nrg4 showed a significantly high area under the curve value (AUC, 0.85; 95% CI, 0.75 to 0.94) with 81.4% sensitivity and 95.3% specificity to identify CAD. Conclusion: Generally, the serum level of Nrg4 declines in patients with CAD, which might be an independent risk factor for CAD.

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The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions

Cited by 9 publications

References 60 publications

Brown fat triglyceride content is associated with cardiovascular risk markers in adults from a tropical region

Brown fat triglyceride content is associated with cardiovascular risk markers in adults from a tropical region

GDF15 is required for cold-induced thermogenesis and contributes to improved systemic metabolic health following loss of OPA1 in brown adipocytes

Implications of the Serum Concentrations of Neuregulin-4 (Nrg4) in Patients with Coronary Artery Disease: A Case-Control Study

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