Sarcolipin knockout mice fed a high‐fat diet exhibit altered indices of adipose tissue inflammation and remodeling

MacPherson, Rebecca E. K.; Gamu, Daniel; Frendo‐Cumbo, Scott; Castellani, L; Kwon, Frenk; Tupling, A. Russell; Wright, David C.

doi:10.1002/oby.21521

Cited by 18 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, by increasing energy demand in muscle through modulation of SERCA activity, SLN acts as an exercise mimetic to increase energy expenditure. In addition, SLN activity can be enhanced by activity (e.g., exercise) and by adaptive thermogenesis in response to cold or caloric excess ( MacPherson et al, 2016 ; Nie et al, 2017 ; Sepa-Kishi et al, 2017 ). Most importantly, we have not found adverse effects due to SLN overexpression in muscle.…”

Section: Discussionmentioning

confidence: 99%

Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism in Skeletal Muscle

et al. 2018

View full text Add to dashboard Cite

The major objective of this study was to understand the molecular basis of how sarcolipin uncoupling of SERCA regulates muscle oxidative metabolism. Using genetically engineered sarcolipin (SLN) mouse models and primary muscle cells, we demonstrate that SLN plays a crucial role in mitochondrial biogenesis and oxidative metabolism in muscle. Loss of SLN severely compromised muscle oxidative capacity without affecting fiber-type composition. Mice overexpressing SLN in fast-twitch glycolytic muscle reprogrammed mitochondrial phenotype, increasing fat utilization and protecting against high-fat diet-induced lipotoxicity. We show that SLN affects cytosolic Ca transients and activates the Ca/calmodulin-dependent protein kinase II (CamKII) and PGC1α axis to increase mitochondrial biogenesis and oxidative metabolism. These studies provide a fundamental framework for understanding the role of sarcoplasmic reticulum (SR)-Ca cycling as an important factor in mitochondrial health and muscle metabolism. We propose that SLN can be targeted to enhance energy expenditure in muscle and prevent metabolic disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism in Skeletal Muscle

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The presence of crown‐like structures was determined as we have described in detail previously (MacPherson et al. ).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were sampled in each image to determine cross-sectional area (>200 cells/mouse) (ImageJ software, National Institute of Mental Health, Bethesda, MD). The presence of crown-like structures was determined as we have described in detail previously (MacPherson et al 2016).…”

Section: Histologymentioning

confidence: 99%

Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

Frendo‐Cumbo

MacPherson

Wright

2016

Physiological Reports

Self Cite

View full text Add to dashboard Cite

The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low‐ (LFD; 10% Kcal from fat) or high‐fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue‐specific insulin signaling were measured 4 weeks post‐treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD. Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin‐stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis.

show abstract

“…( 10 ) ( 86 )]. For example, obese (high-fat-diet [HFD]-fed) sarcolipin deficient mice had shown depot-specific increase in AT inflammation and remodeling by expressing higher levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in the epididymal fat rather than inguinal fat ( 59 ). These gene expression patterns are well correlated with macrophage infiltration and inflammatory activation.…”

Section: Adipose Tissue and Obesitymentioning

confidence: 99%

Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes

Appari

Channon

McNeill

2018

Antioxidants & Redox Signaling

109

View full text Add to dashboard Cite

Significance: Obesity and diabetes are associated with chronic activation of inflammatory pathways that are important mechanistic links between insulin resistance (IR), type 2 diabetes (T2D), and cardiovascular disease pathogenesis. The development of these metabolic diseases is associated with changes in both the number and phenotype of adipose tissue macrophages (ATMs). Emerging lines of evidence have shown that ATMs release proinflammatory cytokines similar to classically activated M1 macrophages, which directly contribute to IR or T2D. In contrast, adipose tissue (AT) from lean healthy individuals contains macrophages with a less inflammatory M2 phenotype.Recent Advances: Recent research has shown that macrophage phenotype is linked to profound changes in macrophage cellular metabolism.Critical Issues: This review focuses on the role of macrophages in AT inflammation and obesity, and the metabolic changes in macrophage function that occur with activation that underpin their role in the pathogenesis of IR and T2D. We highlight current targets for altering macrophage metabolism from both within the field of metabolic disease and AT biology and more widely within inflammatory biology.Future Directions: As our knowledge of macrophage metabolic programming in AT builds, there will be increasing scope for targeting this aspect of macrophage biology as a therapeutic strategy in metabolic diseases. Antioxid. Redox Signal. 29, 297–312.

show abstract

Sarcolipin knockout mice fed a high‐fat diet exhibit altered indices of adipose tissue inflammation and remodeling

Cited by 18 publications

References 41 publications

Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism in Skeletal Muscle

Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism in Skeletal Muscle

Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes

Contact Info

Product

Resources

About