Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of exogenous rGDF11 reduced body weight by 3-17% and significantly improved glucose tolerance in aged mice fed a chow (~30% vs. saline) or HF (~50% vs. saline) diet and young mice fed a HFD (~30%). On the other hand, exogenous rGDF8 showed signifcantly lesser effect or no effect at all on glucose tolerance compared to rGDF11, consistent with data demonstrating that GFD11 is a more potent signaling ligand than GDF8. Collectively, our results show that administration of exogenous rGDF11, but not rGDF8, can reduce diet-induced weight gain and improve metabolic homeostasis. Aging is typically associated with impaired glucose tolerance, insulin resistance, and hepatosteatosis in both mice and humans. These metabolic disorders correlate with increased adiposity 1 , as well as an age-related decline in functional pancreatic β-cell mass (reviewed in 2). Identifying signals that modulate adipose tissue mass, glucose tolerance, insulin sensitivity, and/or functional β-cell mass in aging mammals could provide new targets for treatment of metabolic syndrome and diabetes. We previously showed that rGDF11 administration to aging mice results in a broad range of beneficial effects on brain 3,4 , skeletal muscle 5 , and cardiac tissues 6,7. GDF11 is a circulating blood factor which belongs to the larger transforming growth factor β (TGFβ) superfamily of extracellular ligands. New data published from multiple labs indicate that exogenous delivery of rGDF11 to rodent models of hyperglycemia (e.g. fed a high-fat diet HFD) reduced fasting blood glucose levels and improved glucose tolerance. The mechanism(s) behind these metabolic improvements may be due to a significant, yet transient, reduction in body mass 8-10. In fact, recent data suggests that rGDF11 stimulates secretion of adiponectin and a caloric restriction-like phenotype 10. On the other hand, others have shown that higher dosages of exogenous rGDF11 or viral overexpression of GDF11 via plasmid or viral vector caused cachexia, premature death, and anorexia 11-15. It is possible that these conflicting reports are due to drastically different doses and/or methodology used to artifically raise circulating GDF11 levels. Similarly, opposing results have also been reported regarding how GDF8, also known as myostatin, effects energy balance and metabolism 16-21. GDF8 is classically described as a potent negative regulator of skeletal muscle mass in addition to playin...
Purpose of Review: Notalgia paresthetica (NP) is a chronic cutaneous neuropathy primarily characterized by localized pruritus and associated dysesthesias, including sensations of pain, numbness, and tingling. The sensory neuropathy characteristic of NP is thought to result from spinal nerve entrapment caused by degenerative changes in the spine or musculoskeletal compression. This review summarizes the current medical literature with a focus on the past five years regarding NP, its pathophysiology, presentation, and current treatment options. Recent Findings: Though treatments exist with varying efficacy, to date, there exists no definitive treatment for NP. Treatment options for NP are varied and range from topical and oral agents to interventional procedures and physical therapy. Of the treatments evaluated, topical capsaicin remains the most efficacious treatment for NP. Conclusions: The lack of established treatment guidelines makes treating NP complicated as it dramatically affects patients’ quality of life. Further research with larger sample sizes is needed to evaluate better the most effective treatment and dosing regimen for patients afflicted with NP.
Purpose of Review Meralgia paresthetica (MP) is a condition characterized by paresthesias, neuropathic pain, and alterations in sensorium of the anterolateral thigh secondary to impingement of the lateral femoral cutaneous nerve (LFCN). MP is generally diagnosed by clinical history and is often a diagnosis of exclusion. When diagnosis remains a challenge, diagnostic modalities such as ultrasound, MRI, electromyography, and nerve conduction studies have been utilized as an adjunct. This review summarizes the most recent medical literature regarding MP, its pathophysiology, presentation, and current treatment options. Recent Findings Treatment options for patients with MP range from lifestyle modifications and conservative management to surgical procedures. Initial management is often conservative with symptoms managed with medications. When conservative management fails, the next step is regional blocks followed by surgical management. The conflicting data for treatment options for MP highlight how the evidence available does not point to a single approach that’s universally effective for treating all patients with MP. Summary Despite the apparent success at treating MP with regional blocks and surgical interventions, much remains to be known about the dosing, frequency, and optimal interventions due to the inconclusive results of current studies. Further research including randomized controlled trials are needed to better understand the most optimal treatment options for MP including studies with a larger number of participants.
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