Cover Story Current Issue

Obesity represents a complex medical and behavioural problem which is insufficiently managed by current treatment interventions. Over the past decades, it has become increasing clear that the brain plays a fundamental role in regulating energy balance and body weight homeostasis. Central control of eating and energy balance is determined by a rich interplay of humoral, neuronal and molecular mechanisms.

Henrik H. Hansen, Johanna Perens, Urmas Roostalu, Jacob Lercke Skytte, ... Jacob Hecksher-Sørensen

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Current Issue

Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH

Brian Finan, Sebastian D. Parlee, Bin Yang

Background

Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologiesranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments.

Scope of Review

In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies.

Major Conclusion

Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.

Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH

Brian Finan, Sebastian D. Parlee, Bin Yang

Background

Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologiesranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments.

Scope of Review

In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies.

Major Conclusion

Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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The 8th Helmholtz Diabetes Conference

The 8th Helmholtz Diabetes Conference will take place virtually from May 10th-12th. This year, the conference will focus on the genetic and epigenetic mechanisms involved in the development of diabetes.

For more information and to register, click here.