Dataset Information

Brown adipose tissue uptake of triglyceride-rich lipoprotein-derived fatty acids in diabetic or obese mice under different temperature conditions.

ABSTRACT:

Background

In vivo imaging of glucose analogue 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) via positron emission tomography (PET) is the current gold standard to visualize and assess brown adipose tissue (BAT) activity. However, glucose metabolism is only a part of the metabolic activity of BAT. [¹⁸F]FDG-PET has been shown in clinical trials to often fail to visualize BAT under insulin-resistant conditions associated with aging and weight gain. We employed a novel developed triglyceride-based tracer to visualize BATs metabolic activity under different temperature conditions as well as under diabetic and obese conditions in preclinical models.

Results

[¹⁸F]BDP-TG-chylomicron-like particles visualized BAT in control, streptozocin-induced diabetes and obese mice. Increased BAT tracer uptake was found in control mice acutely exposed to cold but not in cold-acclimated animals. Diabetes did not remove BAT tracer uptake, but did limit BAT tracer uptake to levels of control mice housed at 21 °C. In obese animals, BAT tracer uptake was significantly reduced, although the stimulating effect of cold exposure could still be noted.

Conclusion

BAT was visualized in control, diabetic and obese conditions. Streptozocin-induced diabetes, but not obesity, inhibited the stimulatory effect of cold exposure.

SUBMITTER: Paulus A

PROVIDER: S-EPMC7578207 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Brown adipose tissue uptake of triglyceride-rich lipoprotein-derived fatty acids in diabetic or obese mice under different temperature conditions.

Paulus Andreas A Drude Natascha N van Marken Lichtenbelt Wouter W Mottaghy Felix M FM Bauwens Matthias M

EJNMMI research 20201021 1

<h4>Background</h4>In vivo imaging of glucose analogue 2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose ([<sup>18</sup>F]FDG) via positron emission tomography (PET) is the current gold standard to visualize and assess brown adipose tissue (BAT) activity. However, glucose metabolism is only a part of the metabolic activity of BAT. [<sup>18</sup>F]FDG-PET has been shown in clinical trials to often fail to visualize BAT under insulin-resistant conditions associated with aging and weight gain. We employed ...[more]

PMID: 33085016

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Project description:Background and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1M-CM-^_ and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear. We now aimed to elucidate the mechanism by which caspase-1 deficiency reduces modulates resistance to high fat diet-feeding fat accumulation in adipose tissue by focusing on the role of caspase-1 in the regulation of triglyceride (TG)-rich lipoprotein metabolism. Methods: Caspase-1 deficient and wild-type mice (both C57Bl/6 background) were used to determine postprandial TG kinetics, intestinal TG absorption, VLDL-TG production as well as TG clearance, all of which strongly contribute to the supply of TG for storage in adipose tissue. Micro-array and qPCR analysis were used to unravel intestinal and hepatic metabolic pathways involved. Results: Caspase-1 deficiency reduced the postprandial response to an oral lipid load, while tissue specific clearance of TG-rich lipoproteins was not changed. Indeed, an oral olive oil gavage containing [3H]TG revealed that caspase-1 deficiency significantly decreased intestinal chylomicron-TG production and reduced the uptake of [3H]TG-derived FA by liver, muscle, and adipose tissue. Similarly, caspase-1 deficiency reduced the hepatic VLDL-TG production without reducing VLDL-apoB production, despite an elevated hepatic TG content. Pathway analysis revealed that caspase-1 deficiency reduces intestinal and hepatic expression of genes involved in lipogenesis. Conclusions: Absence of caspase-1 reduces assembly and secretion of TG-rich lipoproteins, thereby reducing the availability of TG-derived FA for uptake by peripheral organs including adipose tissue. We anticipate that caspase-1 represents a novel link between innate immunity and lipid metabolism. Keywords: Expression profiling by array Wild-type (WT) and Casp1-null mice were maintained at lab chow. Animals, aged between 14 and 16 weeks (n=3 per genotype), were killed and liver and intestinal segments were removed. Livers were isolated from mice that were fasted over night, whereas intesines were removed from mice 2 hrs after they received an oral lipid load.Total RNA was isolated and subjected to gene expression profiling.

Project description:BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women's Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women's Health Study; NCT00000479).

Dataset Information

Brown adipose tissue uptake of triglyceride-rich lipoprotein-derived fatty acids in diabetic or obese mice under different temperature conditions.

Background

Results

Conclusion

Publications

Brown adipose tissue uptake of triglyceride-rich lipoprotein-derived fatty acids in diabetic or obese mice under different temperature conditions.

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