High glucose, insulin and free fatty acid concentrations synergistically enhance perilipin 3 expression and lipid accumulation in macrophages

Fan, Bin; Gu, Jianqiu; Rong, Yan; Zhang, Hong; Feng, Juan; Ikuyama, Shoichiro

doi:10.1016/j.metabol.2013.02.013

Cited by 27 publications

(17 citation statements)

References 53 publications

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“…overnight) increases cardiac lipid droplets and TAG content likely due to impaired fatty acid oxidation in the absence of nutritional glucose supply. 59, 235 However, fasting does not lead to reduced heart function; this is further evidence that not all causes of TAG accumulation are detrimental.…”

Section: Metabolic Modulation As a Therapeutic Intervention In Lipotomentioning

confidence: 85%

“…However, analogous to circulating lipoproteins where overexpression of many apolipoproteins including apoC-II that activates lipoprotein lipase (LpL) results in hypertriglyceridemia, 58 excess protein coating of the lipid droplet by amphipathic proteins prevents lipolysis by non-physiologic processes. 51, 52, 59, 60 …”

Section: Cardiac Lipid Accumulation and Storagementioning

confidence: 99%

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Lipid Use and Misuse by the Heart

Schulze

Drosatos

Goldberg

2016

Circulation Research

235

196

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The heart utilizes large amounts of fatty acids as energy providing substrates. The physiologic balance of lipid uptake and oxidation prevents accumulation of excess lipids. Several processes that affect cardiac function including ischemia, obesity, diabetes, sepsis, and most forms of heart failure lead to altered fatty acid oxidation and often also to the accumulation of lipids. There is now mounting evidence associating certain species of these lipids with cardiac lipotoxicity and subsequent myocardial dysfunction. Experimental and clinical data are discussed and paths to reduction of toxic lipids as a means to improve cardiac function are suggested.

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Section: Metabolic Modulation As a Therapeutic Intervention In Lipotomentioning

confidence: 85%

Section: Cardiac Lipid Accumulation and Storagementioning

confidence: 99%

Lipid Use and Misuse by the Heart

Schulze

Drosatos

Goldberg

2016

Circulation Research

235

196

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“…Metabolic syndrome and T2D are associated with increased serum glucose, FFA, and insulin levels and accelerated atherosclerosis. Glucose, FFA, and insulin have been demonstrated to enhance conversion of macrophages to foam cell in vitro by increasing perilipin 3 expression 217 . RVX000222 is a BET inhibitor which has advanced to phase III clinical trial examining time to major cardiovascular events for patients with high risk T2D (NCT02586155).…”

Section: Therapeutic Implications Of Macrophage Biologymentioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

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Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

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“…A model of high glucose and lipids has been used widely in cultured cells to mimic the metabolic derangements that occur in DM [19]. In addition, hypoxia is a well-established feature of ischemic CVD [20].…”

Section: Introductionmentioning

confidence: 99%