Serum Autotaxin/<scp>ENPP</scp>2 correlates with insulin resistance in older humans with obesity

Reeves, Valerie L.; Trybuła, J; Wills, Rachel C.; Goodpaster, Bret H.; Dubé, John J.; Kienesberger, Petra C.; Kershaw, Erin E.

doi:10.1002/oby.21232

Cited by 57 publications

(55 citation statements)

References 33 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…() found a small but positive correlation between BMI and ATX mass, but not with ATX enzymatic activity, whereas Reeves et al. () did not find any correlation, except when adjusting for sex. Moreover, Reeves et al.…”

Section: Discussionmentioning

confidence: 92%

“…Moreover, Reeves et al. () did not find any correlation between BMI and ATX expression in visceral and subcutaneous fat. Similar to Reeves et al.…”

Section: Discussionmentioning

confidence: 93%

“…ATX has been shown to be involved in obesity and impaired glucose metabolism, in both human (Reeves et al. ) and animal models (Rancoule et al. ), but the impact of severe obesity and the effect of massive AT loss on ATX levels has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Acute and chronic effect of bariatric surgery on circulating autotaxin levels

et al. 2019

View full text Add to dashboard Cite

Autotaxin ( ATX ), an adipose tissue‐derived lysophospholipase, has been involved in the pathophysiology of cardiometabolic diseases. The impact of bariatric surgery on circulating ATX levels is unknown. We examined the short‐ (24 h, 5 days) and longer‐term (6 and 12 months) impact of bariatric surgery; as well as the short‐term effect of caloric restriction ( CR ) on plasma ATX levels in patients with severe obesity. We measured ATX levels in 69 men and women (mean age: 41 ± 11 years, body mass index: 49.8 ± 7.1 kg/m 2 ), before and after biliopancreatic diversion with duodenal switch surgery ( BPD ‐ DS ) as well as in a control group (patients with severe obesity without surgery; n = 34). We also measured ATX levels in seven patients with severe obesity and type 2 diabetes who underwent a 3‐day CR protocol before their BPD ‐ DS . At baseline, ATX levels were positively associated with body mass index, fat mass, insulin resistance ( HOMA ‐ IR ) as well as insulin and leptin levels and negatively with fat‐free mass. ATX concentrations decreased 26.2% at 24 h after BPD ‐ DS (342.9 ± 152.3 pg/mL to 253.2 ± 68.9 pg/mL, P < 0.0001) and by 16.4% at 12 months after BPD ‐ DS (342.9 ± 152.3 pg/mL to 286.8 ± 182.6 pg/mL, P = 0.04). ATX concentrations were unchanged during follow‐up in the control group ( P = 0.4), and not influenced by short‐term CR . In patients with severe obesity, bariatric surgery induced a rapid and sustained decrease in plasma ATX levels. Acute changes in ATX may not be explained by bariatric surgery‐induced CR .

show abstract

Section: Discussionmentioning

confidence: 92%

“…Moreover, Reeves et al. () did not find any correlation between BMI and ATX expression in visceral and subcutaneous fat. Similar to Reeves et al.…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Acute and chronic effect of bariatric surgery on circulating autotaxin levels

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This peptide performed better in predicting glucose metabolism and cortical thickness than ENPP2 SYPEILTLK in preliminary stepwise regression analyses. To confirm that autotaxin reflected central dysmetabolism, established metabolic and inflammatory biomarkers in CSF were regressed against autotaxin, including insulin-like growth factor binding protein 2 (IGFBP2) peptides, pyruvate kinase isozymes M1/M2, neurosecretory protein VGF, fructose-bisphosphate aldolase A, cholecystokinin and IL-6 receptor [31, 32]. These were the only metabolic or metabolic-related indices available in the CSF for ADNI.…”

Section: Methodsmentioning

confidence: 99%

Autotaxin is Related to Metabolic Dysfunction and Predicts Alzheimer’s Disease Outcomes

McLimans

Willette

2017

JAD

View full text Add to dashboard Cite

Background Obesity and insulin resistance are associated with neuropathology and cognitive decline in Alzheimer’s disease (AD). Objective Ecto-nucleotide pyrophosphatase/phosphodiesterase 2, also called autotaxin, is produced by beige adipose tissue, regulates metabolism, and is higher in AD prefrontal cortex (PFC). Autotaxin may be a novel biomarker of dysmetabolism and AD. Methods We studied Alzheimer’s Disease Neuroimaging Initiative participants who were cognitively normal (CN; n=86) or had mild cognitive impairment (MCI; n=135) or AD (n=66). Statistical analyses were conducted using SPSS software. Multinomial regression analyses tested if higher autotaxin was associated with higher relative risk for MCI or AD diagnosis, compared to the CN group. Linear mixed model analyses were used to regress autotaxin against MRI, FDG-PET, and cognitive outcomes. Spearman correlations were used to associate autotaxin and CSF biomarkers due to non-normality. FreeSurfer 4.3 derived mean cortical thickness in medial temporal lobe and prefrontal regions of interest. Results Autotaxin levels were significantly higher in MCI and AD. Each point increase in log-based autotaxin corresponded to a 3.5 to 5 times higher likelihood of having MCI and AD, respectively. Higher autotaxin in AD predicted hypometabolism in the medial temporal lobe [R2=0.343, p<0.001] and PFC [R2=0.294, p<0.001], and worse performance on executive function and memory factors. Autotaxin was associated with less cortical thickness in PFC areas like orbitofrontal cortex [R2=0.272, p<0.001], as well as levels of total tau, p-tau181, and total tau/Aβ1–42. Conclusions These results are comparable to previous reports using insulin resistance. CSF autotaxin may be a useful dysmetabolism biomarker for examining AD outcomes and risk.

show abstract

“…In humans, increased mRNA expression of autotaxin in fat and elevated circulating autotaxin has also been observed in obese patients with insulin resistance and glucose intolerance compared to those with normal glucose tolerance . Furthermore, circulating levels of autotaxin correlate positively with insulin resistance in older humans, and are an independent predictor for non‐alcoholic fatty liver disease . Several insulin resistance‐inducing factors, including interleukin‐6 (IL‐6), glucose and insulin, induce the expression and secretion of autotaxin in inflammatory status .…”

Section: Introductionmentioning

confidence: 99%

Autotaxin/lysophosphatidic acid signaling mediates obesity‐related cardiomyopathy in mice and human subjects

Weng

Jiang

Ding

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Obesity is associated with increased cardiovascular morbidity and mortality, but the direct signals to initiate or exaggerate cardiomyopathy remain largely unknown. Present study aims to explore the pathophysiological role of autotaxin/lysophosphatidic acid (LPA) in the process of cardiomyopathy during obesity. Through utilizing mouse model and clinical samples, present study investigates the therapeutic benefits of autotaxin inhibitor and clinical correlation to obesity‐related cardiomyopathy. The elevated circulating levels of autotaxin are closely associated with cardiac parameters in mice. Administration with autotaxin inhibitor, PF‐8380 effectively attenuates high fat diet‐induced cardiac hypertrophy, dysfunction and inflammatory response. Consistently, autotaxin inhibition also decreases circulating LPA levels in obese mice. In in vitro study, LPA directly initiates cell size enlargement and inflammation in neonatal cardiomyocytes. More importantly, circulating levels of autotaxin are positively correlated with cardiac dysfunction and hypertrophy in 55 patients. In conclusion, present study uncovers the correlation between circulating autotaxin and cardiac parameters in mice and human patient, and provided solid evidence of the therapeutic application of autotaxin inhibitor in combating obesity‐related cardiomyopathy.

show abstract

Serum Autotaxin/ENPP2 correlates with insulin resistance in older humans with obesity

Cited by 57 publications

References 33 publications

Acute and chronic effect of bariatric surgery on circulating autotaxin levels

Acute and chronic effect of bariatric surgery on circulating autotaxin levels

Autotaxin is Related to Metabolic Dysfunction and Predicts Alzheimer’s Disease Outcomes

Autotaxin/lysophosphatidic acid signaling mediates obesity‐related cardiomyopathy in mice and human subjects

Contact Info

Product

Resources

About