Nature Reviews Endocrinology

At the time of its first clinical application 100 years ago, insulin was presented as the cure for people with diabetes mellitus. That transpired to be an overstatement, yet insulin has proven to be the lifesaver for people with type 1 diabetes mellitus and an essential therapy for many with type 2 diabetes mellitus or other forms of diabetes mellitus. Since its discovery, insulin (a molecule of only 51 amino acids) has been the subject of pharmaceutical research and development that has paved the way for other protein-based therapies. From purified animal-extracted insulin and human insulin produced by genetically modified organisms to a spectrum of insulin analogues, pharmaceutical laboratories have strived to tailor the preparations to the needs of patients. Nonetheless, overall glycaemic control often remains poor as exogenous insulin is still not able to mimic the physiological insulin profile. Circumventing subcutaneous administration and the design of analogues with profiles that mimic that of physiological insulin are ongoing areas of research. Novel concepts, such as once-weekly insulins or glucose-dependent and oral insulins, are on the horizon but their real-world effectiveness still needs to be proven. Until a true cure for type 1 diabetes mellitus is found and the therapeutic arsenal for other forms of diabetes mellitus is expanded, insulin will remain central in the treatment of many people living with diabetes mellitus.

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The evolving view of thermogenic adipocytes — ontogeny, niche and function

Farnaz Shamsi, Chih-Hao Wang & Yu-Hua Tseng

doi : 10.1038/s41574-021-00562-6

Nature Reviews Endocrinology volume 17, pages726–744 (2021)

The worldwide incidence of obesity and its sequelae, such as type 2 diabetes mellitus, have reached pandemic levels. Central to the development of these metabolic disorders is adipose tissue. White adipose tissue stores excess energy, whereas brown adipose tissue (BAT) and beige (also known as brite) adipose tissue dissipate energy to generate heat in a process known as thermogenesis. Strategies that activate and expand BAT and beige adipose tissue increase energy expenditure in animal models and offer therapeutic promise to treat obesity. A better understanding of the molecular mechanisms underlying the development of BAT and beige adipose tissue and the activation of thermogenic function is the key to creating practical therapeutic interventions for obesity and metabolic disorders. In this Review, we discuss the regulation of the tissue microenvironment (the adipose niche) and inter-organ communication between BAT and other tissues. We also cover the activation of BAT and beige adipose tissue in response to physiological cues (such as cold exposure, exercise and diet). We highlight advances in harnessing the therapeutic potential of BAT and beige adipose tissue by genetic, pharmacological and cell-based approaches in obesity and metabolic disorders.

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Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis

Omar Al-Massadi, Carlos Dieguez, Marc Schneeberger, Miguel López, Markus Schwaninger, Vincent Prevot & Ruben Nogueiras

doi : 10.1038/s41574-021-00559-1

Nature Reviews Endocrinology volume 17, pages745–755 (2021)

Melanin-concentrating hormone (MCH) is a small cyclic peptide expressed in all mammals, mainly in the hypothalamus. MCH acts as a robust integrator of several physiological functions and has crucial roles in the regulation of sleep–wake rhythms, feeding behaviour and metabolism. MCH signalling has a very broad endocrine context and is involved in physiological functions and emotional states associated with metabolism, such as reproduction, anxiety, depression, sleep and circadian rhythms. MCH mediates its functions through two receptors (MCHR1 and MCHR2), of which only MCHR1 is common to all mammals. Owing to the wide variety of MCH downstream signalling pathways, MCHR1 agonists and antagonists have great potential as tools for the directed management of energy balance disorders and associated metabolic complications, and translational strategies using these compounds hold promise for the development of novel treatments for obesity. This Review provides an overview of the numerous roles of MCH in energy and glucose homeostasis, as well as in regulation of the mesolimbic dopaminergic circuits that encode the hedonic component of food intake.

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Paracetamol use during pregnancy — a call for precautionary action

Ann Z. Bauer, Shanna H. Swan, David Kriebel, Zeyan Liew, Hugh S. Taylor, Carl-Gustaf Bornehag, Anderson M. Andrade, Jørn Olsen, Rigmor H. Jensen, Rod T. Mitchell, Niels E. Skakkebaek, Bernard Jégou & David M. Kristensen

doi : 10.1038/s41574-021-00553-7

Nature Reviews Endocrinology volume 17, pages757–766 (2021)

Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.

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