Macrophages influencing fat cell conversion.

Unlocking Your Metabolism: How Macrophages Influence Fat Burning

Rhea Morgan in Health & Wellness June 2025 • 4 min read.

"Discover the surprising role of immune cells in converting white fat to brown fat and boosting your body's energy expenditure."

In the ongoing quest to understand and optimize our metabolism, scientists are constantly uncovering new layers of complexity. One fascinating area of research focuses on beige adipocytes – specialized fat cells within white adipose tissue (WAT) that can burn energy through a process called 'browning.' This process is stimulated by the sympathetic nervous system and can be a key target in the fight against obesity.

A recent study sheds light on the unexpected role of macrophages, a type of immune cell, in influencing this browning process. Conducted on mice, the research reveals that macrophages can either promote or inhibit the conversion of white fat to brown fat, depending on their type and location within the body. This discovery could pave the way for innovative approaches to manipulate fat metabolism and improve overall metabolic health.

Brown adipose tissue (BAT) is a specialized tissue for thermogenic energy expenditure, in contrast to white adipose tissue (WAT) that stores excessive energy as triglycerides [1, 2]. BAT thermogenesis depends on uncoupling protein 1 (UCP1), a mitochondrial protein abundantly expressed in brown adipocytes, which dissipates the proton gradient that normally drives the synthesis of cellular ATP. The thermogenic activity of UCP1 is controlled by the sympathetic nervous system

The Yin and Yang of Macrophages in Fat Metabolism

Macrophages influencing fat cell conversion.

The study, led by researchers in Japan, investigated why some areas of WAT are more prone to browning than others. They observed that inguinal WAT (found in the groin area) in mice readily converted to beige fat upon exposure to cold temperatures, while perigonadal WAT (around the reproductive organs) remained stubbornly white.

Intriguingly, they found a higher concentration of macrophages in perigonadal WAT compared to inguinal WAT. Further investigation revealed that cold exposure activated pro-inflammatory M1 macrophages in perigonadal WAT. These M1 macrophages appeared to hinder the browning process. Conversely, when the researchers depleted macrophages, using clodronate, they observed enhanced browning in perigonadal WAT.

The key findings of the study include:

Cold exposure induces UCP1 expression (a marker for beige fat) in inguinal WAT, but not perigonadal WAT.
Perigonadal WAT has a higher concentration of macrophages than inguinal WAT.
Cold exposure activates M1 macrophages in perigonadal WAT.
Depletion of macrophages enhances cold-induced UCP1 expression in perigonadal WAT.

These results suggest that M1 macrophages are involved in the phenotype of perigonadal WAT that hardly undergo browning. This is because sympathetic stimulation induces beige adipocytes in white adipose tissue (WAT), known as browning of WAT. In this study, exposure of mice to cold ambient temperature (10 °C) for 24 h induced the mRNA expression of uncoupling protein 1 (UCP1), a marker for beige adipocytes, in inguinal WAT, but not in perigonadal WAT.

Implications and Future Directions

This research adds another layer of complexity to our understanding of fat metabolism. It highlights the intricate interplay between the immune system and adipose tissue and suggests that manipulating macrophage activity could be a potential strategy for promoting browning and improving metabolic health. Further research is needed to determine how these findings translate to humans and to explore the specific mechanisms by which M1 macrophages inhibit browning. However, this study opens up exciting new avenues for tackling obesity and related metabolic disorders.

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This article is based on research published under:

DOI-LINK: 10.1007/s12576-017-0567-3, Alternate LINK

Title: Role Of Macrophages In Depot-Dependent Browning Of White Adipose Tissue

Subject: Physiology

Journal: The Journal of Physiological Sciences

Publisher: Springer Science and Business Media LLC

Authors: Ken Machida, Yuko Okamatsu-Ogura, Woongchul Shin, Shinya Matsuoka, Ayumi Tsubota, Kazuhiro Kimura

Published: 2017-09-06

Everything You Need To Know

What role do macrophages play in the conversion of white fat to brown fat?

Macrophages, a type of immune cell, play a crucial role in the browning of white adipose tissue (WAT). The research indicates that the presence and type of macrophages can either promote or inhibit the conversion of white fat to beige fat, influencing overall metabolic health. Specifically, M1 macrophages in perigonadal WAT appear to hinder the browning process.

How do white adipose tissue (WAT) and brown adipose tissue (BAT) differ in their function and energy expenditure?

White adipose tissue (WAT) and brown adipose tissue (BAT) differ significantly in their function. WAT primarily stores excess energy as triglycerides, while BAT is specialized for thermogenic energy expenditure, burning energy to produce heat. The conversion of WAT to beige fat, also known as browning, involves the expression of uncoupling protein 1 (UCP1), enabling energy expenditure instead of storage.

What differences were observed between inguinal WAT and perigonadal WAT in terms of browning and macrophage concentration?

The study revealed that inguinal WAT, found in the groin area of mice, readily converted to beige fat upon cold exposure, indicated by UCP1 expression. In contrast, perigonadal WAT, located around the reproductive organs, resisted this conversion. Researchers observed a higher concentration of M1 macrophages in perigonadal WAT, which seemed to inhibit the browning process.

What is uncoupling protein 1 (UCP1) and what role does it play in energy expenditure and beige fat formation?

Uncoupling protein 1 (UCP1) is a mitochondrial protein predominantly found in brown adipocytes and beige adipocytes. It plays a crucial role in thermogenesis by dissipating the proton gradient that normally drives ATP synthesis. This process generates heat, contributing to energy expenditure. The expression of UCP1 is a key marker for beige fat and indicates the browning of white adipose tissue (WAT).

What are the implications of M1 macrophages inhibiting the browning process, and how could this be targeted for therapeutic intervention?

The presence of M1 macrophages inhibits the browning process in perigonadal WAT. This suggests that manipulating macrophage activity could be a potential therapeutic strategy for promoting browning and improving metabolic health. Further research is needed to understand the specific mechanisms by which M1 macrophages inhibit browning and how these findings can be translated to humans. Targeting M1 macrophages could lead to new interventions for obesity and related metabolic disorders.