Opposing Effects of Adiponectin Receptors 1 and 2 on Energy Metabolism

Bjursell, Mikael; Ahnmark, Andrea; Bohlooly‐Y, Mohammad; William-Olsson, Lena; Rhedin, Magdalena; Peng, Xiao-Rong; Ploj, Karolina; Gerdin, Anna-Karin; Arnerup, Gunnel; Elmgren, Anders; Berg, Anna‐Lena; Oscarsson, Jan; Lindén, Daniel

doi:10.2337/db06-1432

Cited by 254 publications

(240 citation statements)

References 52 publications

(69 reference statements)

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“…Additionally, it was found that IPo improved mitochondrial function, reduced oxidative stress, and increased nitric oxide levels in an adiponectin-dependent manner. Mechanistically, the beneficial effects of adiponectin in IPo appeared to be specifically mediated by the activation of adiponectin receptor 1 (AdipoR1) but not by AdipoR2, thereby confirming previous results demonstrating that AdipoR1 and AdipoR2 may regulate different mechanisms (7). Of note, IPo also increased the interaction between AdipoR1 and caveolin-3 (Cav3), a protein that appears to be critical for AdipoR1 function.…”

supporting

confidence: 85%

The Importance of Restoring the Adiponectin Signaling Pathway to Reduce Myocardial Reperfusion Injury in Diabetes

Sciarretta

Frati

2016

Diabetes

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supporting

confidence: 85%

The Importance of Restoring the Adiponectin Signaling Pathway to Reduce Myocardial Reperfusion Injury in Diabetes

Sciarretta

Frati

2016

Diabetes

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“…The most simple interpretation of this observation is that there would be a corresponding reduction in the availability of these receptors to bind adiponectin and a subsequent decline in gAdand fAd-stimulated effects. Many, but not all, studies in animal models [44] and humans [13,14] have also suggested an important role for alterations in ADIPORs in the pathogenesis of insulin resistance and diabetes. Of particular interest, Adipor1 −/− mice showed increased Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Representative western blots are shown, with quantitative data expressed as means±SEM of at least three independent experiments. *p<0.05 with respect to control adiposity associated with decreased glucose tolerance and energy expenditure, whereas Adipor2 −/− mice were lean and resistant to high-fat diet-induced obesity [44]. In human studies, Steinberg's group has shown that skeletal muscle from obese or obese type 2 diabetic patients showed decreased sensitivity to gAd, yet ADIPOR1 levels were higher, suggesting that aspects downstream of the receptor may inhibit adiponectin action [13].…”

Section: Discussionmentioning

confidence: 99%

Leptin prevents the metabolic effects of adiponectin in L6 myotubes

et al. 2009

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Aims/hypothesis Adiponectin and leptin are negatively and positively correlated with human obesity respectively, and have both been shown to regulate energy metabolism in skeletal muscle. However, little is known about their signalling and functional crosstalk. Here we investigated the effects of leptin on metabolic actions of (1) globular adiponectin (gAd) and (2) full-length adiponectin (fAd) in L6 cells. Methods Glucose uptake was measured upon gAd and fAd treatment after incubation with different doses (0.3, 0.6, 3, 6, 60 nmol/l) of leptin for 6, 12 and 24 h. We also measured adiponectin receptor (ADIPOR) expression and stimulation of downstream signalling by gAd and fAd using coimmunoprecipitation and western blotting following leptin pretreatment, as well as analysis of fatty acid uptake and oxidation using radiolabelled tracers. Results Leptin attenuated the stimulation of glucose uptake by gAd and fAd in a dose-and time-dependent manner, a finding correlated with decreased levels of ADIPOR1 and ADIPOR2. gAd and fAd increased palmitate uptake via activation of AMP protein kinase (T172), enhanced expression of the fatty acid transporter CD36, phosphorylated acetyl-CoA carboxylase (S79) and enhanced palmitate oxidation, all of which were attenuated by leptin pretreatment. Adiponectin can also enhance insulin sensitivity via direct signalling crosstalk; here we show that enhanced insulin-stimulated IRS-1 (Y612) and Akt (T308) phosphorylation in response to fAd was attenuated by leptin. APPL1 was recently identified as a critical mediator of adiponectin action in skeletal muscle. We demonstrated that leptin attenuated binding of APPL1 to LKB1, a downstream target leading to AMPK phosphorylation. Conclusions/interpretation The direct metabolic and insulin-sensitising effects of adiponectin were attenuated in the presence of leptin.

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“…Expression of adipoR1 has previously been reported to increase during conditions of increased fat oxidation and insulin sensitivity, including weight loss (39) and aerobic exercise training (40), and we speculate that the downregulation of adipoR1 may be a mechanism by which high-fat diet induces insulin resistance. A recent study examining the effects of knockout of adipoR supports this because knockout of adipoR1 increased adiposity and insulin resistance, whereas knockout of adipoR2 increased insulin sensitivity and prevented high-fat diet-induced obesity (41). In rodents, both AdipoR1 and adipoR2 expression are reduced in response to refeeding (42).…”

Section: Figmentioning

confidence: 94%

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

et al. 2007

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Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n ‫؍‬ 8) and in ageand fatness-matched individuals with a strong family history of type 2 diabetes (n ‫؍‬ 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P < 0.05). This was related to impaired activation of genes involved in lipid metabolism, including those for peroxisome proliferator-activated receptor coactivator-1␣ (PGC1␣) and fatty acid translocase (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased 23% after the high-fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1␣ and FAT/CD36 are likely candidates in mediating this response. Diabetes 56: [2046][2047][2048][2049][2050][2051][2052][2053] 2007 R elatives of individuals with type 2 diabetes are an ideal human model to test for mechanisms in the early development of insulin resistance because approximately two-thirds eventually develop diabetes, and they can be tested before the development of other confounding factors, including hyperglycemia, dyslipidemia, and changes in insulin secretion (1). Insulin-resistant relatives will also develop impaired lipid metabolism, including increased circulating free fatty acids (FFAs) (2), accumulation of triglycerides and other lipid moieties within skeletal muscle (3), and postprandial hypertriglyceridemia (4). However, the mechanism(s) responsible for these early defects in lipid metabolism is not completely elucidated, although we and others suggest that intramuscular triglyceride accumulation may occur secondary to the development of insulin resistance (3,5).In lean individuals, increasing the proportion of dietary fat switches on fatty acid oxidation, whereas the infusion of glucose and insulin promotes carbohydrate oxidation. The cellular capacity to switch from lipid to carbohydrate and vice versa has been termed "metabolic flexibility," and there is large variation in this parameter between individuals (6). Obese and weight-reduced obese individuals have impaired metabolic flexibility on a whole-body level (7). Fatty acid...

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Opposing Effects of Adiponectin Receptors 1 and 2 on Energy Metabolism

Cited by 254 publications

References 52 publications

The Importance of Restoring the Adiponectin Signaling Pathway to Reduce Myocardial Reperfusion Injury in Diabetes

The Importance of Restoring the Adiponectin Signaling Pathway to Reduce Myocardial Reperfusion Injury in Diabetes

Leptin prevents the metabolic effects of adiponectin in L6 myotubes

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

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