Raspberry alleviates obesity-induced inflammation and insulin resistance in skeletal muscle through activation of AMP-activated protein kinase (AMPK) α1 - PubMed (original) (raw)

Raspberry alleviates obesity-induced inflammation and insulin resistance in skeletal muscle through activation of AMP-activated protein kinase (AMPK) α1

Liang Zhao et al. Nutr Diabetes. 2018.

Abstract

Objective: Through dynamic means, etiological factors, including chronic inflammation and insulin resistance have the potential to perpetuate metabolic incidences such as type 2 diabetes and obesity. Abatement of such syndromes can be achieved by complex mechanisms initiated through bioactive compounds such as polyphenols derived from fruits. Using a whole-fruit approach, the effects of dietary red raspberry, which is rich in polyphenols, on inflammatory responses and insulin resistance in the skeletal muscles of Mus musculus were studied along with the potential role of AMP-activated protein kinase (AMPK) to act as a key mediator.

Subjects: Wild-type (WT) mice and mice deficient in the catalytic subunit (α1) of AMPK (AMPKα1-/-) were fed with a high-fat diet (HFD) or HFD supplemented with raspberry (5% dry weight) for 10 weeks. Factors involved in inflammatory responses, insulin signaling transduction, and mitochondrial biogenesis were evaluated.

Results: Dietary raspberry reduced ectopic lipid storage, alleviated inflammation responses, improved whole-body insulin sensitivity, and promoted mitochondrial biogenesis in the skeletal muscle of WT mice, but not AMPKα1-/- mice.

Conclusions: AMPKα1 is an important mediator for the beneficial effects of raspberry through alleviating inflammatory responses and sensitizing insulin signaling in skeletal muscle of HFD-fed mice.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1

Fig. 1

Contents of total AMPKα (a) and phospho-AMPKα (b) in the Gastrocnemius muscle of wild-type (WT) and AMPKα1 knockout mice with/without raspberry supplementation. (**P < 0.01, *P < 0.05, HFD + RAS vs. HFD only for each genotype as determined by unpaired two-tailed Student’s t test; mean ± s.d.; n = 6). t total content, p phosphorylated form

Fig. 2

Fig. 2. Muscle weight and ectopic lipid accumulation in the skeletal muscle of wild-type (WT) and AMPKα1 knockout mice with/without raspberry supplementation.

a Tibialis anterior muscle weight. b Gastrocnemius muscle weight. c Total triacylglycerol content in Gastrocnemius muscle. d Masson trichrome staining of Tibialis anterior (top: ×200 magnification; bottom: ×400 magnification) and relative area of fat (e) and collagen (f). (**P < 0.01, *P < 0.05, HFD + RAS versus HFD only for each genotype as determined by unpaired two-tailed Student’s t test; mean ± s.d.; n = 6)

Fig. 3

Fig. 3. Inflammatory response in the Gastrocnemius muscle of wild-type (WT) and AMPKα1 knockout mice with/without raspberry supplementation.

a Quantitative PCR analysis of Tnfα, Il1β, Il6 and Il18 expression. b Western blots of t-p65 and p-p65 and their relative contents. c Western blots of t-JNK and p-JNK and their relative contents. (**P < 0.01, *P < 0.05, HFD + RAS vs. HFD only for each genotype as determined by unpaired two-tailed Student’s t test; mean ± s.d.; n = 6). t total content, p phosphorylated form

Fig. 4

Fig. 4. Expression of Glucose transport 4 (GLUT4) and relative contents of insulin signaling proteins in the Gastrocnemius muscle of wild-type (WT) and AMPKα1 knockout mice with/without raspberry supplementation.

a Quantitative PCR analysis of Glut4 expression. b Western blots of Glut4 and their relative contents. c Western blots of insulin signaling proteins (t-AKT, p-AKT, t-PKCθ and p-PKCθ) and their relative contents. (**P < 0.01, *P < 0.05, HFD + RAS versus HFD only for each genotype as determined by unpaired two-tailed Student’s t test; mean ± s.d.; n = 6), t total content, p phosphorylated form

Fig. 5

Fig. 5. Mitochondria biogenesis in the Gastrocnemius muscle of wild-type (WT) and AMPKα1 knockout mice with/without raspberry supplementation.

a Western blots cytochrome C (Cyt C) and its relative contents. b Quantitative PCR analysis of Pgc1α, Nrf1, Cpt1, Tfam and Cycs. (**P < 0.01, *P < 0.05, HFD + RAS versus HFD only for each genotype as determined by unpaired two-tailed Student’s t test; mean ± s.d.; n = 6)

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References

    1. Mullen W, et al. Ellagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties. J. Agric. Food Chem. 2002;50:5191–5196. doi: 10.1021/jf020140n. - DOI - PubMed
    1. Burton-Freeman BM, Sandhu AK, Edirisinghe I. Red raspberries and their bioactive polyphenols: cardiometabolic and neuronal health links. Adv. Nutr.: Int. Rev. J. 2016;7:44–65. doi: 10.3945/an.115.009639. - DOI - PMC - PubMed
    1. Luo T, Miranda-Garcia O, Adamson A, Sasaki G, Shay N. Development of obesity is reduced in high-fat fed mice fed whole raspberries, raspberry juice concentrate, and a combination of the raspberry phytochemicals ellagic acid and raspberry ketone. J. Berry Res. 2016;6:213–223. doi: 10.3233/JBR-160135. - DOI
    1. Petersen KF, Shulman GI. Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus. Am. J. Cardiol. 2002;90:11–18. doi: 10.1016/S0002-9149(02)02554-7. - DOI - PubMed
    1. Hardie DG, Sakamoto K. AMPK: A key sensor of fuel and energy status in skeletal muscle. Physiology. 2006;21:48–60. doi: 10.1152/physiol.00044.2005. - DOI - PubMed

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