Physiology and pathophysiology of adipose tissue

This Review discusses the current understanding of adipose tissue macrophages and T cells. Discussion of these cells is used as an example of how metabolic tissue niches can dictate immune cell function in unique ways that diverge from the classic understanding of leukocyte biology.

This Review examines the origins of marrow adipocytes and their function under normal or pathological conditions. Regulation of bone marrow adipose tissue by nutrient status is considered, as well as the interactions between bone marrow adipose tissue, haematopoietic cells of the bone marrow and the bone.

Mammals are highly susceptible to being permanently influenced by maternal factors and nutritional status during the intrauterine and early postnatal periods. This Review summarizes and discusses the potential role of several adipokines, including leptin and adiponectin, in inducing metabolic programming through their effects during development.

Understanding of intermuscular adipose tissue has expanded over the past few years. This Review discusses the specific role of intermuscular adipose tissue in metabolic diseases in humans and in animal models, with a particular emphasis on the quantity and biological properties of this unique adipose tissue.

A new study by Reverte-Salisa and colleagues identifies a molecular mechanism through which the cAMP-mediating protein EPAC1 controls the size of brown and beige adipose tissue. This finding opens the door for the development of pharmacological interventions to prevent the decline of brown adipose tissue in obesity and ageing, and thereby improve metabolic health.

Tissue-resident stem cells have a central role in tissue regeneration, but other accessory cells are also required for efficient regeneration. A new study by Sastourné-Arrey and colleagues reveals a delicate mechanism of skeletal muscle regeneration through an unexpected type of inter-organ communication, in which stromal cells derived from adipose tissue support muscle regeneration.

Adipose tissue is a complex organ that has crucial endocrine and metabolic functions in mammalian physiology. A new Article Series aims to collate adipose tissue content from Nature Reviews Endocrinology and provide a useful resource for researchers working in this field.

The field of bioenergetics is rapidly expanding with new discoveries of mechanisms and potential therapeutic targets. The 2023 Keystone symposium on ‘Bioenergetics in Health and Disease’, which was jointly held with the symposium ‘Adipose Tissue: Energizing Good Fat’, consisted of a powerhouse line-up of researchers who shared their insights.

Adipose tissue is highly versatile, dynamic and essential for metabolic health. In 2022, several exciting discoveries provided a high-resolution view of cellular composition and cell–cell communication within the adipose niche, and revealed how adipose tissue communicates with other organs and modulates metabolism during normal and pathophysiological states.

Adipocyte insulin resistance is a driving force for systemic insulin resistance. Advances in human stem cell culture have established conditions for human adipocytes that give rise to a reproducible population of adipocytes that retain a high level of insulin sensitivity, paving the way for high throughput screening approaches.

By identifying a new means of communication between endothelial cells and adipocytes, researchers provide evidence that the endothelial cells actively provoke lipid release from adipocytes to support capillary growth. This crosstalk ultimately helps to maintain metabolic health in obesity.

There is growing evidence that fat accumulation in the pancreas can have consequences for metabolic health. This Review discusses the methods for detecting pancreatic fat and the potential causes and pathogenic consequences of pancreatic fat accumulation.

By mapping the spatial organization of adipose tissue, Bäckdahl and colleagues identify adipocyte progenitor structures as well as three subclasses of adipocytes with different molecular functions, including insulin sensitivity and leptin signalling.

This Review highlights the ontogeny of thermogenic adipocytes, regulation of the adipose tissue microenvironment and inter-organ communication between adipose and other tissues. In addition, activation of thermogenic adipose tissue in humans and animal models is discussed, as well as the therapeutic potential of thermogenic adipose tissue.

Adipose tissue macrophages (ATMs) have important roles in the regulation of inflammatory responses and insulin resistance in obesity. A new study reports that a subpopulation of ATMs, TIM4⁺ resident ATMs, modulate adipocyte size via platelet-derived growth factor-CC production during development and diet-induced adipose tissue expansion.

Harnessing the thermogenic, energy-expending capacity of adipocytes has the potential to combat metabolic disorders. Although β₃-adrenergic receptor agonists are the best-known activators of thermogenesis, they carry considerable cardiovascular risks. A new study demonstrates the ability of G protein-coupled receptor 3 to intrinsically drive adipose thermogenesis independent of β₃-adrenergic receptor signalling.

A new study investigates brown adipose tissue (BAT) volume in young, metabolically healthy adults. The focus is on the associations between BAT volume and BMI, waist circumference, whole-body adipose tissue mass, visceral adipose tissue mass and cold-induced BAT activity. Of note, the reported associations differed in men and women.

White adipocyte metabolism is important for the regulation of systemic metabolism and is often dysregulated in various conditions, such as cancer and type 2 diabetes mellitus. In this Review, Langin and colleagues provide an overview of lipid metabolism in white adipocytes and the related metabolism of glucose and discuss how these pathways provide therapeutic targets in metabolic disorders.

This Review highlights how obesity and impaired metabolic health increase complications and mortality in coronavirus disease 2019 (COVID-19) and summarizes the consequences of infection with severe acute respiratory syndrome coronavirus 2 for organ function. In addition, there is a discussion on the implications of the COVID-19 pandemic for the obesity pandemic.