The Leu7Pro polymorphism of the signal peptide of neuropeptide Y (NPY) gene is associated with increased levels of inflammatory markers preceding vascular complications in patients with type 2 diabetes

Jaakkola, Ulriikka; Kakko, Tanja; Seppälä, Helena; Vainio-Jylhä, Elina; Vahlberg, Tero; Raitakari, Olli T.; Kallio, Johanna

doi:10.1016/j.mvr.2010.07.010

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…Recently, it was reported that there is a gender difference in the NPY-mediated effects of the P7 allele. [81] The associations of the p.L7P seem to be more pronounced in men than women, which is in agreement with the findings in OE-NPY DBH mice indicating that males develop more severe metabolic changes. The mouse also models the vascular diseases associated with the p.L7P, as it has been associated with hypertension[182] and shown to increase the risk of atherosclerotic vascular disease in middle-aged men,[83] patients with hypertension[84] and in type 1 and type 2 diabetic patients.…”

Section: Clinical Relevancesupporting

confidence: 89%

Neuropeptide Y in the noradrenergic neurons induces the development of cardiometabolic diseases in a transgenic mouse model

Ruohonen

Pesonen²,

Savontaus

2012

Indian J Endocr Metab

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Neuropeptide Y (NPY) is a neuropeptide widely expressed in the brain and a peptide transmitter of sympathetic nervous system (SNS) co-released with noradrenaline (NA) in prolonged stress. Association of a gain-of-function polymorphism in the human NPY gene with dyslipideamia, diabetes and vascular diseases suggests that increased NPY plays a role in the pathogenesis of the metabolic syndrome in humans. In the hypothalamus, NPY plays an established role in the regulation of body energy homeostasis. However, the effects of NPY elsewhere in the brain and in the SNS are less explored. In order to understand the role of NPY co-expressed with NA in the sympathetic nerves and brain noradrenergic neurons, a novel mouse model overexpressing NPY in noradrenergic neurons was generated. The mouse displays metabolic defects such as increased adiposity, hepatosteatosis, and impaired glucose tolerance as well as stress-related hypertension and increased susceptibility to vascular wall hypertrophy. The mouse phenotype closely reflects the findings of the several association studies with human NPY gene polymorphisms, and fits with the previous work on the effects of stress-induced NPY release on metabolism and vasculature. Thus, in addition of promoting feeding and obesity in the hypothalamus, NPY expressed in the noradrenergic neurons in the brain and in the SNS induces the development of cardiometabolic diseases.

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Section: Clinical Relevancesupporting

confidence: 89%

Neuropeptide Y in the noradrenergic neurons induces the development of cardiometabolic diseases in a transgenic mouse model

Ruohonen

Pesonen²,

Savontaus

2012

Indian J Endocr Metab

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“…Another possibility for the change in NPY levels after smoking could be the increased carbohydrate intake (57). A third possibility, given that increased NPY plasma levels are found in insulin resistant states, such as type 2 diabetes, obesity, and hypertension (58,59), is that NPY is increased as a consequence of increased insulin resistance observed in our study participants. Last, given that NPY is found to be produced in pancreatic b cells and to inhibit insulin secretion in vitro (60,61), it is conceivable that changes in NPY could reflect the alteration in b-cell function following smoking cessation.…”

Section: Appetite After Smoking Cessationmentioning

confidence: 87%

Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite

Stadler

Tomann

Storka

et al. 2014

European Journal of Endocrinology

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Objective: To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, b-cell function, and appetite. Subjects and methods: Twenty-seven long-term smokers (nZ27; nine females/18 males, 28G1 years, 22.9G0.6 kg/m 2 )attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; nZ14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and b-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured. Results: After O3 months' smoking abstinence, body weight, and fat mass were increased (C4 and C22% respectively, P!0.05) and fasting insulin sensitivity deteriorated (QUICKI: post, 0.37G0.02 vs baseline, 0.41G0.2; P!0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after O3 months' smoking abstinence (P!0.01). Carbohydrate ingestion increased after stopping smoking (P!0.05). NPY fasting levels were increased after O3 months (P!0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged. Conclusion: Smoking cessation is associated with transient metabolic changes including increased b-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.

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“…Thus, NPY role in appetite, diet‐related fat, oxidation, and metabolic risk (Alkemade et al, ; Aschbacher et al, ; Ilhan et al, ; Katsiki et al, ; Pankov, Chekhranova, & Karpova, ) may increase appetite‐related effects, thereby leading to T2D and Mets (Pankov et al, ). NPY is associated with inflammation in T2D (Jaakkola et al, ), T2D (Nordman et al, ), MetS (Pesonen, ), atherosclerosis (Kakko, Jaakkola, Raitakari, & Kallio, ), and MetS‐CAD (Parizadeh et al, ).…”

Section: Prl‐pathway Genes Mental Diseases and Metabolic Genetic Ovmentioning

confidence: 99%

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

Postolache

Bosque-Plata

Jabbour

et al. 2019

American J of Med Genetics Pt B

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Schizophrenia (SCZ) and major depressive disorder (MDD) in treatment-naive patients are associated with increased risk for type 2 diabetes (T2D) and metabolic syndrome (MetS). SCZ, MDD, T2D, and MetS are often comorbid and their comorbidity increases cardiovascular risk: Some risk genes are likely co-shared by them. For instance, transcription factor 7-like 2 (TCF7L2) and proteasome 26S subunit, non-ATPase 9 (PSMD9) are two genes independently reported as contributing to T2D and SCZ, and PSMD9 to MDD as well. However, there are scarce data on the shared genetic risk among SCZ, MDD, T2D, and/or MetS. Here, we briefly describe T2D, MetS, SCZ, and MDD and their genetic architecture. Next, we report separately about the comorbidity of SCZ and MDD with T2D and MetS, and their respective genetic overlap. We propose a novel hypothesis that genes of the prolactin (PRL)-pathway may be implicated in the comorbidity of these disorders. The inherited predisposition of patients with SCZ and MDD to psychoneuroendocrine dysfunction may confer increased risk of T2D and MetS. We illustrate a strategy to identify risk variants in each disorder and in their comorbid psychoneuroendocrine and mentalmetabolic dysfunctions, advocating for studies of genetically homogeneous and phenotype-rich families. The results will guide future studies of the shared predisposition and molecular genetics of new homogeneous endophenotypes of SCZ, MDD, and metabolic impairment.

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The Leu7Pro polymorphism of the signal peptide of neuropeptide Y (NPY) gene is associated with increased levels of inflammatory markers preceding vascular complications in patients with type 2 diabetes

Cited by 16 publications

References 46 publications

Neuropeptide Y in the noradrenergic neurons induces the development of cardiometabolic diseases in a transgenic mouse model

Neuropeptide Y in the noradrenergic neurons induces the development of cardiometabolic diseases in a transgenic mouse model

Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

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