Lipidomic profiling of plasma free fatty acids in type-1 diabetes highlights specific changes in lipid metabolism

Sobczak, Amélie Isabelle Sylvie; Pitt, Samantha J.; Smith, Terry; Ajjan, Ramzi; Stewart, Alan J.

doi:10.1016/j.bbalip.2020.158823

Cited by 19 publications

(13 citation statements)

References 41 publications

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“…Although FFA is an important link between obesity, insulin resistance, and type 2 diabetes, little is known about their levels in T1D. A recent study conducted in patients with T1D identified an increase in the ratio of saturated to unsaturated FFA compared to nondiabetic controls ( 53 ). Despite this increase, total FFA in the serum of T1D patients was lower compared to the control group ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Tree Shrew Model of Diabetic Retinopathy

et al. 2022

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Existing animal models with rod-dominant retinas have shown that hyperglycemia injures neurons, but it is not yet clearly understood how blue cone photoreceptors and retinal ganglion cells (RGCs) deteriorate in patients because of compromised insulin tolerance. In contrast, northern tree shrews (Tupaia Belangeri), one of the closest living relatives of primates, have a cone-dominant retina with short wave sensitivity (SWS) and long wave sensitivity (LWS) cones. Therefore, we injected animals with a single streptozotocin dose (175 mg/kg i.p.) to investigate whether sustained hyperglycemia models the features of human diabetic retinopathy (DR). We used the photopic electroretinogram (ERG) to measure the amplitudes of A and B waves and the photopic negative responses (PhNR) to evaluate cone and RGC function. Retinal flat mounts were prepared for immunohistochemical analysis to count the numbers of neurons with antibodies against cone opsins and RGC specific BRN3a proteins. The levels of the proteins TRIB3, ISR-1, and p-AKT/p-mTOR were measured with western blot. The results demonstrated that tree shrews manifested sustained hyperglycemia leading to a slight but significant loss of SWS cones (12%) and RGCs (20%) 16 weeks after streptozotocin injection. The loss of BRN3a-positive RGCs was also reflected by a 30% decline in BRN3a protein expression. These were accompanied by reduced ERG amplitudes and PhNRs. Importantly, the diabetic retinas demonstrated increased expression of TRIB3 and level of p-AKT/p-mTOR axis but reduced level of IRS-1 protein. Therefore, a new non-primate model of DR with SWS cone and RGC dysfunction lays the foundation to better understand retinal pathophysiology at the molecular level and opens an avenue for improving the research on the treatment of human eye diseases.

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Section: Discussionmentioning

confidence: 99%

A Novel Tree Shrew Model of Diabetic Retinopathy

et al. 2022

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“…Other elements measured were Elongase (oleate/palmitate); steaoryl-coA desaturase indices (palmitoleate/palmitate and oleate/stearate) in both cases were significantly increased in BTBR ob/ob vs. WT (0.11 vs. 0.16 p = 0.009) and 7.12 vs. 27.7 p < 0.0001). In contrast delta-(5)-desaturase (D5D) index (arachidonate/dihomo-γ-linolenate) significant variation was only observed in the STZ group (9.5 vs. 12.75 p = 0.001) [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice

Opazo-Ríos

Soto-Catalán

Lázaro

et al. 2022

IJMS

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Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4–22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.

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“…Thus, one or both pathways may contribute to ceramide formation, which can be used for sphingomyelin synthesis via sphingomyelin synthase. Interestingly, patients with type 1 diabetes also show changes in the profile of fatty acids in circulation, where they in turn overwhelm muscle, liver, heart, and other peripheral organs and tissues [ 52 ]. This may explain why we observed in the liver a decrease in the sphingosine content.…”

Section: Discussionmentioning

confidence: 99%

Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats

Pérez-Villavicencio

Flores‐Estrada

Franco

et al. 2022

IJMS

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The profile of sphingomyelin and its metabolites shows changes in the plasma, organs, and tissues of patients with cardiovascular, renal, and metabolic diseases. The objective of this study was to investigate the effect of empagliflozin on the levels of sphingomyelin and its metabolites, as well as on the activity of acid and neutral sphingomyelinase (aSMase and nSMase) and neutral ceramidase (nCDase) in the plasma, kidney, heart, and liver of streptozotocin-induced diabetic and Angiotensin II (Ang II)-induced hypertension rats. Empagliflozin treatment decreased hyperglycemia in diabetic rats whereas blood pressure remained elevated in hypertensive rats. In diabetic rats, empagliflozin treatment decreased sphingomyelin in the plasma and liver, ceramide in the heart, sphingosine-1-phosphate (S1P) in the kidney, and nCDase activity in the plasma, heart, and liver. In hypertensive rats, empagliflozin treatment decreased sphingomyelin in the plasma, kidney, and liver; S1P in the plasma and kidney; aSMase in the heart, and nCDase activity in the plasma, kidney, and heart. Our results suggest that empagliflozin downregulates the interaction of the de novo pathway and the catabolic pathway of sphingolipid metabolism in the diabetes, whereas in Ang II-dependent hypertension, it only downregulates the sphingolipid catabolic pathway.

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Lipidomic profiling of plasma free fatty acids in type-1 diabetes highlights specific changes in lipid metabolism

Cited by 19 publications

References 41 publications

A Novel Tree Shrew Model of Diabetic Retinopathy

A Novel Tree Shrew Model of Diabetic Retinopathy

Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice

Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats

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