Glucolipotoxicity promotes the capacity of the glycerolipid/NEFA cycle supporting the secretory response of pancreatic beta cells

Oberhauser, Lucie; Jiménez‐Sánchez, Cecilia; Madsen, Jesper Grud Skat; Duhamel, Dominique; Mandrup, Susanne; Brun, Thierry; Maechler, Pierre

doi:10.1007/s00125-021-05633-x

Cited by 18 publications

(9 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionsupporting

confidence: 56%

“…PFD in the pathogenesis of T2DM and its clinical relevance are being valued and becoming a research hotspot. 13 Our study provided evidence on QCT could serve as a reliable technique in quantifying PFD in patients with T2DM, and we found that high PFD positively correlated with the degree of insulin resistance and may play an important role in islet cell dysfunction in the late-stage T2DM. [14][15][16][17] It has been reported in the literature that long-term exposure to a high-fat diet leads to interlobular and intralobular fat accumulation, inflammatory cell infiltration, and pancreatic fibrosis in rat pancreas, thereby impairing normal pancreatic architecture, resulting in pancreatic fat fibrosis and impaired islet function.…”

Section: Discussionsupporting

confidence: 56%

“…However, recent studies showed a controversial result on fat deposited in the pancreas may help maintain insulin secretion and slow the onset of T2DM by promoting the capacity of glycerolipid/NEFA cycling thereby helping β cells to deal with glucotoxic conditions. 13 These different findings may be attributed by the different exposure duration of the pancreas to excessive fat, and also indicate that PFD may play differential roles in early or late stage T2DM.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Quantitative Assessment of Pancreatic Fat by Quantitative CT in Type 2 Diabetes Mellitus

Li¹,

Yue²,

Chen³

et al. 2022

IJGM

View full text Add to dashboard Cite

Objective To characterize the pancreatic fat deposition (PFD) in patients with type 2 diabetes mellitus (T2DM) by quantitative computed tomography (QCT) and investigate the relationship between PFD and clinical metabolic parameters and islet function. Materials and Methods A total of 150 patients with T2DM and 93 age-matched healthy subjects underwent QCT to quantify PFD were included. PFD and various biochemical parameters were correlated by statistical methods and multiple stepwise linear regression modeling. Results PFD measured by QCT in the T2DM group was statistically higher than that in the healthy control group, and the pancreatic CT value was statistically lower than that in the control group. The QCT measured PFD was negatively correlated with the pancreatic CT values (P < 0.001), and positively correlated with triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), visceral fat area (VAT) and insulin resistance index (HOMA-IR) (P < 0.05) in the T2DM patients. Multiple stepwise linear regression analysis identified PFD as the dependent variable factor for T2DM. Conclusion This study suggests QCT as a reliable technique in measuring PFD in T2DM. High PFD is positively correlated with the degree of insulin resistance and may play an important role in islet cell dysfunction in T2DM.

show abstract

Section: Discussionsupporting

confidence: 56%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Assessment of Pancreatic Fat by Quantitative CT in Type 2 Diabetes Mellitus

Li¹,

Yue²,

Chen³

et al. 2022

IJGM

View full text Add to dashboard Cite

show abstract

“…Indeed, the sequestration of palmitate, the most abundant saturated fatty acid found in human serum, in the form of neutral lipids was found to protect the cells against palmitate-mediated apoptosis in multiple studies [ 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. Exposure of the unsaturated fatty acid, oleate, prevented palmitate-induced apoptosis by promoting the incorporation of palmitate into triglycerides in CHO-, 1.1B4-, and INS1e cells, with increased intracellular neutral lipid accumulation [ 81 , 82 , 83 ]. In addition to oleate, the polyunsaturated fatty acid, C20:4 arachidonic acid, was also reported to have a similar beneficial impact on C2C12 cells, a mouse skeletal muscle cell line [ 84 ].…”

Section: Lipid Droplet Biogenesis: a Potential Protective Mechanism A...mentioning

confidence: 99%

Ceramide Acyl Chain Length and Its Relevance to Intracellular Lipid Regulation

Zheng

Ali

2022

IJMS

View full text Add to dashboard Cite

Ceramides are a class of sphingolipids which are implicated in skin disorders, obesity, and other metabolic diseases. As a class with pleiotropic effects, recent efforts have centred on discerning specific ceramide species and their effects on atopic dermatitis, obesity, type 2 diabetes, and cardiovascular diseases. This delineation has allowed the identification of disease biomarkers, with long acyl chain ceramides such as C16- and C18-ceramides linked to metabolic dysfunction and cardiac function decline, while ultra-long acyl chain ceramides (>25 carbon acyl chain) were reported to be essential for maintaining a functional skin barrier. Given the intricate link between free fatty acids with ceramides, especially the de novo synthetic pathway, intracellular lipid droplet formation is increasingly viewed as an important mechanism for preventing accumulation of toxic ceramide species. Here, we review recent reports of various ceramide species involved in skin abnormalities and metabolic diseases, and we propose that promotion of lipid droplet biogenesis can be seen as a potential protective mechanism against deleterious ceramides.

show abstract

“…154,162 In Although obesity has traditionally been considered a major risk factor for the occurrence of T2DM, an increasing number of published studies have found that the mortality of T2DM patients with obesity is lower. 6,168 Oberhauser et al 169 found that stored lipids enable pancreatic β-cell to adapt to chronic glucolipotoxic conditions by upregulating genes associated with the glycerolipid/NEFA cycle. The cycle of fat storage/mobilization enables β-cell to adapt to excess glucose and preserve part of the secretory response, suggesting that when the body uses fat as an energy source, the release of fat may instead be protective against T2DM.…”

Section: Beneficial Effects Of Adipose Tissue On the Cardiovascular S...mentioning

confidence: 99%

Two‐sided roles of adipose tissue: Rethinking the obesity paradox in various human diseases from a new perspective

et al. 2022

View full text Add to dashboard Cite

Summary Overweight and obesity, as a result of excess fat accumulation, have become a worldwide public health issue. Recent studies have shown that obesity is closely related to many human diseases, such as cancer, cardiovascular diseases, and type 2 diabetes mellitus, in which adipose tissue plays a dual role. In addition to thermal and mechanical insulation and a critical role in energy storage and heat production, adipose tissue is also a highly plastic endocrine and signaling organ that secretes multiple bioactive molecules for inter‐organ crosstalk. The phenotypic and biological changes of adipose tissue under pathological conditions, especially in obesity, increase the challenge of deciphering the positive or negative effects of adipose tissue in disease. Despite numerous studies on obesity and adipose tissue, the ambiguous role of adipose tissue on specific organs or tissues in different diseases is not fully understood, and the definite mechanisms remain obscure. In this review, we first summarize the basic biological characteristics of adipose tissue in the physiological state and the abnormal remodeling of adipose tissue during obesity. We then discuss the complex and disparate effects of obesity on various human diseases, with a particular focus on the dual roles and underlying mechanisms of adipose tissue, a quintessential player in obesity, in this process. More importantly, rethinking the causes of the “obesity paradox” phenomenon in diseases from the perspective of adipose homeostasis and dysfunction provides a novel strategy for disease treatment by intervening in fat function.

show abstract

Glucolipotoxicity promotes the capacity of the glycerolipid/NEFA cycle supporting the secretory response of pancreatic beta cells

Cited by 18 publications

References 49 publications

Quantitative Assessment of Pancreatic Fat by Quantitative CT in Type 2 Diabetes Mellitus

Quantitative Assessment of Pancreatic Fat by Quantitative CT in Type 2 Diabetes Mellitus

Ceramide Acyl Chain Length and Its Relevance to Intracellular Lipid Regulation

Two‐sided roles of adipose tissue: Rethinking the obesity paradox in various human diseases from a new perspective

Contact Info

Product

Resources

About