Cited by 425Adipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and LipoproteinsCardiovascular Disease and Adiposity

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Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

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Thorp, Alicia A., Schlaich, Markus P.·2015·Journal of Diabetes Research

DOI 10.1155/2015/341583PMC PMC4430650

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Abstract

Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.

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“In addition to this, circadian rhythm disturbances would trigger an inter-organ imbalance of sympathetic-parasympathetic branches, and sympathetic overactivity is a recognized risk factor for obesity and insulin resistance, which may further increase the risk of NAFLD (59, 60).”
Background
Independent association of resting energy expenditure with blood pressure: confirmation in populations of the African diaspora
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“Some investigators have likewise argued that increased sympathetic activity secondary to hyperinsulinemia is a feature of the obesity syndrome [48, 49].”
Background
The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy—A Review
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Background
Coupling of energy intake and energy expenditure across a temperature spectrum: impact of diet-induced obesity in mice
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Dietary salt intake predicts future development of metabolic syndrome in the general population
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Pharmacotherapeutic strategies for treating hypertension in patients with obesity
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“thetic nerve activity contributing substantially to arterial hypertension in obesity [18,19].”
BackgroundSelf-citation
The autonomic nervous system in the regulation of glucose and lipid metabolism
Wangler, S., Jarczok, M. N., Ennis, M., Herhaus, B., Wagner, R., Sehgal, R., & Heni, M. (2026) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01221-w · Cited by 17
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“Of particular interest is the observation that, within populations suffering from PTSD, there is the recurrent theme of disrupted glucose metabolism and increased abdominal obesity (Cohen et al., 2009; Li et al., 2016; Rosenbaum et al., 2015; Thorp and Schlaich, 2015).”
Background
Weekly Osteopathic Manipulative Treatment to Improve Measures of Sympathetic Tone in Women With Polycystic Ovary Syndrome: A Randomized, Controlled Pilot Study
Davis, S., Hendryx, J., Menezes, C., Bouwer, S., Menezes, H., Patel, V., Bostick-Smith, C. A., & Speelman, D. L. (2020) · Journal of Osteopathic Medicine · doi:10.7556/jaoa.2020.051 · Cited by 16
The Relationship between Autonomic Regulation of Cardiovascular Function and Body Composition
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Microbial DNA Enrichment Promotes Adrenomedullary Inflammation, Catecholamine Secretion, and Hypertension in Obese Mice
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Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects
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Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging
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“…a role in the development of metabolic disorders, including obesity and type 2 diabetes mellitus (Carnethon et al., 2003, Schlaich et al., 2015, Thorp and Schlaich, 2015), and interestingly autonomic dysfunction is common in patients with several forms of cognitive impairment, including mild…”
High-Fat Diet Modulates the Excitability of Neurons within the Brain–Liver Pathway
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“Increased sympathetic activity is recognized in obese and diabetic conditions and plays a significant role in the development and/or progression of diseases associated with dysregulated glucose homeostasis [3,4].”
Background
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“Hyperuricemia is also closely associated with obesity and can trigger systemic in ﬂ ammation and activate the RAAS and sympathetic nervous systems (29, 30).”
Background
Effect of Intraoperative Goal-Directed Fluid Management on Tissue Oxygen Tension in Obese Patients: a Randomized Controlled Trial
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“Additionally, studies suggest that increased central sympathetic activity plays a pivotal role in the etiology [12] and complications [13] of obesity-related metabolic disorders.”
BackgroundResult
How Perturbated Metabolites in Diabetes Mellitus Affect the Pathogenesis of Hypertension?
Ning, Z., Song, Z., Wang, C., Peng, S., Wan, X., Liu, Z., & Lü, A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.705588 · Cited by 15
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Splenic Leukocytes Get the Nerves up for Myelopoiesis
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“32 Adipose tissue secretes sym-pathoexcitatory leptin and many inﬂammatory cytokines including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-a (TNF-a ), interleukin-6 (IL-6), and C-reactive protein.”
Maternal dyslipidemia during pregnancy and lactation increases blood pressure and disrupts cardiorespiratory and glucose hemostasis in female rat offspring
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Background
Pyridostigmine attenuated high‐fat‐diet induced liver injury by the reduction of mitochondrial damage and oxidative stress via α7nAChR and M3AChR
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“This process, termed “browning”, has raised hope in finding new therapeutic strategies in obesity, by increasing the thermogenic potential of WAT and thus total energy expenditure, forcing lipid mobilization and adiposity reduction.”
BackgroundInfluential
2-Methoxyestradiol ameliorates metabolic syndrome-induced hypertension and catechol-O-methyltransferase inhibited expression and activity in rats
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“Evidences are suggesting that abdominal obesity is related to high sympathetic nerve activity which probably mediated by elevated leptin and insulin levels [13, 14].”
Background
Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress
Dalmasso, C., Leachman, J. R., Ghuneim, S., Ahmed, N., Schneider, E. R., Thibault, O., Osborn, J. L., & Loria, A. S. (2021) · Hypertension · doi:10.1161/hypertensionaha.121.17298 · Cited by 14
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“Common comorbidities in HF such as diabetes and obesity are associated with chronic activation of the sympathetic nervous system [74].”
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Transient Receptor Potential (TRP) based polypharmacological combination stimulates energy expending phenotype to reverse HFD-induced obesity in mice
Kaur, J., Singh, D. P., Kumar, V., Kaur, S., Bhunia, R. K., Kondepudi, K. K., Kuhad, A., & Bishnoi, M. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121704 · Cited by 12
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Remote Monitoring of Sympathovagal Imbalance During Sleep and Its Implications in Cardiovascular Risk Assessment: A Systematic Review
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A subset of neurons in the paraventricular nucleus of the hypothalamus directly project to liver-related premotor neurons in the ventrolateral medulla
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“Evidence supports a positive correlation between metabolic syndrome and excess sympathetic and RAAS activation.(19,20) By preferentially constricting the efferent arteriole, AngII leads to intraglomerular hypertension, which contributes to nephropathy.”
Background
Neurotransmitter Alterations in Prediabetes and Type 2 Diabetes Mellitus: A Narrative Review
Ahrițculesei, R.-V., Boldeanu, L., Dijmărescu, A. L., Assani, M.-Z., Boldeanu, M. V., Siloşi, I., & Vere, C. C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167847 · Cited by 12

Authors: Thorp, A. A., & Schlaich, M. P.
Affiliations: Baker Heart and Diabetes Institute (AU)
Corresponding author: Schlaich, Markus P.
ORCID: Schlaich, Markus P.
Venue: Journal of Diabetes Research
Publisher: Wiley
Published: 2015
Volume: 2015
Pages: 1-11
ISSN: 2314-6745 (ISSN-L)
2314-6753
DOI: 10.1155/2015/341583
PMC: PMC4430650
OpenAlex: W2066041574
Cited by: 425
References: 101
Citations by year: 2026: 28 · 2025: 42 · 2024: 36 · 2023: 44 · 2022: 40 · 2021: 45 · 2020: 48 · 2019: 40 · 2018: 33 · 2017: 31 · 2016: 32 · 2015: 5
FWCI: 4.38
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (unspecified)
Locations: Journal of Diabetes Research (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Health and Medical Research Council
Victorian Government’s Operational Infrastructure Support Program
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: sympathetic nervous system, sympathetic hyperactivity, obesity, metabolic syndrome, energy homeostasis, abdominal obesity, insulin resistance, baroreflex sensitivity, hyperinsulinemia, adipokines, type 2 diabetes, cardiovascular disease, sympathetic activity, device therapy
MeSH terms: Animals, Humans, Obesity, Sympathetic Nervous System, Metabolic Syndrome

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Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

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