A research team at Cincinnati Children’s has uncovered a shared and unexpected repair process that may help the body recover from several kinds of muscle damage. The findings were published online on Nov. 21, 2025, in Current Biology. The project was led by first author Gyanesh Tripathi, PhD, and corresponding author Michael Jankowski, PhD, who oversees the Research Division in Cincinnati Children’s Department of Anesthesia and serves as Associate Director of Basic Science Research for the Pediatric Pain Research Center.

The newly identified mechanism involves macrophages, a type of immune cell. These cells are usually known for acting like tiny cleanup crews that remove bacteria, dead cells, and other unwanted material.

A Neuron-Like Repair Signal

“The biggest surprise about this was finding that a macrophage has a synaptic-like property that delivers an ion to a muscle fiber to facilitate its repair after an injury,” Jankowski says. “It’s literally like the way a neuron works, and it’s working in an extremely fast synaptic-like fashion to regulate repair.”

Scientists have long known that macrophages respond to muscle injury by releasing cytokines and chemokines that create inflammation, influence pain, and help drive the growth and regeneration of muscle fibers.

Searching for Pain Relief Leads to a Different Breakthrough

The research team originally aimed to uncover ways to ease pain during recovery after surgery. They were looking for clues that could eventually reduce the need for pain medications that carry significant side effects.

Although they did not find a new approach for pain relief, they identified a process that makes muscle repair occur more quickly. This discovery may support the development of future treatments for muscle wasting and acute injuries. The findings also suggest that macrophages might eventually serve as specialized “delivery vehicles” for cell-based therapies targeting a wider range of medical conditions.

“These are infiltrating macrophages, a very specific type. They’re not ones already residing in the tissue. These come in after damage occurs,” Jankowski says.

Real-Time Evidence of Rapid Muscle Activation

In experiments that used mouse models of two different injury types, researchers examined how macrophages interact with the myofibers that form muscle tissue. They were even able to capture key moments of this activity as it occurred.

By using brief bursts of a designer chemical to activate the macrophages, the team observed these immune cells forming synaptic-like contacts with myofibers. The macrophages then released calcium ions directly to the muscle fibers, accelerating early stages of healing. Within 10 to 30 seconds, the researchers measured bursts of electrical activity inside the damaged muscle.

“This occurs in a very rapid fashion. You can activate the macrophage and make the muscle twitch subtly almost immediately,” Jankowski says.

Healing Effects Seen in Both Injury and Disease Models

The same type of macrophage-driven signaling also helped mice with disease-like muscle damage. After recognizing the injury, the immune cells gathered at the site and triggered waves of activity in the muscle fibers. After 10 days, mice that received this treatment had substantially more new muscle fibers than mice in the control group.

“A similar synaptic-like response worked in both scenarios,” Jankowski says.

Next Research Steps

More work is needed to determine whether human macrophages behave the same way when muscle is injured. If they do, researchers will still need to learn how to guide or control the process in ways that could be safely used as therapy.

The team is also interested in an unexpected outcome: although the infiltrating macrophages sped up healing, they did not appear to reduce acute pain. Understanding why this occurs may help explain why about 20% of children who undergo surgery continue to experience lingering pain afterward.

Looking ahead, the researchers want to explore whether macrophages can deliver other helpful signals or materials to muscle cells.

Cincinnati Children’s co-authors include Adam Dourson, PhD, Fabian Montecino-Morales, PhD, Jennifer Wayland, MS, Sahana Khanna, Megan Hofmann, Hima Bindu Durumutla, MS, Thirupugal Govindarajan, PhD, Luis Queme, MD, PhD, and Douglas Millay, PhD. The Bioanalysis and Imaging Facility at Cincinnati Children’s also contributed to the work.

Funding for this research came from grants provided by the National Institutes of Health (R01NS105715, R01NS113965, R61/R33AR078060, R01AR068286, R01AG082697) and the Cincinnati Children’s Hospital Research Foundation.

• A major three paper Series in The Lancet finds that ultra-processed foods (UPFs) are rapidly replacing fresh and minimally processed meals around the world. The evidence links rising UPF intake to poorer diet quality and higher risks of multiple chronic diseases.
• The authors explain that although more research on UPFs will continue to be valuable, the current science is already strong enough to justify immediate public health action. Waiting for further studies would allow UPFs to gain an even stronger hold in global diets.
• The Series stresses that improving diets cannot fall solely on individual behavior. Real progress requires coordinated policies that limit UPF production, marketing, and availability, while also addressing high levels of fat, sugar and salt in the food supply and expanding access to healthy food.
• The authors describe UPFs as products of an industrial food system built around corporate profit rather than nutrition or sustainability. They warn that only a united international response can counter the political influence of UPF companies, which remains the biggest obstacle to effective dietary policy reform.

Rising UPF Consumption Sparks Global Health Concerns

A new three paper Series in The Lancet, written by 43 international experts, warns that the rapid spread of ultra-processed foods (UPFs) across global diets is creating a serious public health challenge. The authors detail how UPF companies use a range of strategies to increase sales and block policies designed to protect consumers. The Series offers a plan for stronger government action, greater community involvement, and broader access to affordable, nutritious foods.

Professor Carlos Monteiro, University of Sao Paulo, Brazil, explains, “The growing consumption of ultra-processed foods is reshaping diets worldwide, displacing fresh and minimally processed foods and meals. This change in what people eat is fueled by powerful global corporations who generate huge profits by prioritizing ultra-processed products, supported by extensive marketing and political lobbying to stop effective public health policies to support healthy eating.”

Calls for Strong, Coordinated Policy Action

Professor Camila Corvalan, University of Chile, Chile, adds, “Addressing this challenge requires governments to step up and introduce bold, coordinated policy action — from including markers of UPFs in front-of-package labels to restricting marketing and implementing taxes on these products to fund greater access to affordable, nutritious foods.”

Dr. Phillip Baker, University of Sydney, Australia, continues, “We need a strong global public health response — like the coordinated efforts to challenge the tobacco industry. Including safeguarding policy spaces from political lobbying and building powerful coalitions to advocate for healthy, fair and sustainable food systems and stand-up to corporate power.”

UPFs, based on the Nova classification, are industrially produced branded foods created from low cost ingredients such as hydrogenated oils, protein isolates or glucose/fructose syrup, along with cosmetic additives (e.g. dyes, artificial sweeteners, emulsifiers). These products are intentionally formulated and promoted to replace fresh foods and traditional meals, while maximizing profits for manufacturers (for a detailed definition see paper 1, panel 1).

Research Shows Clear Links Between UPFs and Chronic Disease

The first paper in The Lancet Series reviews scientific evidence gathered since the Nova classification was developed by Prof Carlos Monteiro and colleagues in 2009. The findings consistently show that UPFs are crowding out traditional dietary patterns, lowering overall diet quality, and contributing to higher risks of many chronic diseases.

National surveys also reveal substantial increases in UPF consumption (paper 1, figure 1). The proportion of dietary energy from UPFs tripled in Spain (11% to 32%) and China (4% to 10%) over the past three decades, and rose from 10% to 23% in Mexico and Brazil during the previous forty years. In the USA and UK, levels have remained above 50% for the past two decades, with slight increases over time.

Growing Body of Evidence Underscores Health Risks

The Series reports that diets high in UPFs are associated with overeating, poor nutrient balance (too much sugar and unhealthy fats, too little fibre and protein), and greater exposure to potentially harmful additives. A systematic review of 104 long-term studies found that 92 showed higher risks for at least one chronic disease, with meta-analyses identifying significant associations with 12 health conditions including obesity, type 2 diabetes, cardiovascular disease, depression, and premature death (paper 1, figure 4, appendix p23-24).

While the authors acknowledge scientific debates about Nova and UPF definitions — including the need for more long-term trials, clearer mechanisms, and recognition of product subgroups with differing nutritional qualities — they emphasize that further research should not delay immediate public health action.

Professor Mathilde Touvier, French National Institute for Health and Medical Research (Inserm), France, states, “While healthy debate about UPFs within the scientific community is welcomed, this should be distinguished from attempts by vested interests to undermine the current evidence. The growing body of research suggests diets high in ultra-processed foods are harming health globally and justifies the need for policy action.”

Policy Solutions to Reduce UPFs and Improve Diet Quality

The second paper in the Series outlines policy options to curb UPF production, marketing, and consumption, holding major companies accountable for promoting unhealthy diets (paper 2, table 1). These recommendations are intended to strengthen existing legislation targeting high fat, salt and sugar (HFSS) foods.

Professor Barry Popkin, University of North Carolina, US, says “We call for including ingredients that are markers of UPFs (eg, colors, flavors, and sweeteners) in front-of-package labels, alongside excessive saturated fat, sugar, and salt, to prevent unhealthy ingredient substitutions, and enable more effective regulation.”

Marketing Restrictions, School Policies, and Fresh Food Access

The authors recommend stronger marketing limits, particularly for promotions aimed at children, digital advertising, and brand-level marketing. They also suggest banning UPFs in public settings such as schools and hospitals, and capping shelf space for UPFs in supermarkets. One example of successful reform is Brazil’s national school feeding program, which has removed most UPFs and will require 90% of school food to be fresh or minimally processed by 2026 (paper 2, panel 4).

Alongside regulation, the authors highlight the need to expand access to fresh foods. Taxing selected UPFs could help support subsidies for healthier options, particularly for low-income households.

Professor Marion Nestle, New York University, US, notes, “Improving diets worldwide requires policies tailored to each country’s unique situation and how entrenched UPFs have become in people’s daily eating habits. While priorities may differ, urgent action is needed everywhere to regulate ultra-processed foods alongside existing efforts to reduce high fat, salt, and sugar content.”

Associate Professor Gyorgy Scrinis, University of Melbourne, Australia, adds, “Importantly, policies must ensure that fresh and minimally processed foods are accessible and affordable — not just for those with time to cook, but for busy families and individuals who rely on convenient options. Only by combining stricter regulation on poor quality food products with realistic support for more nutritious choices can we truly promote better diets for all.”

How Corporate Power Drives the Global UPF Boom

The third paper shows that the sharp rise in UPF consumption is being driven primarily by global food corporations rather than individual behavior. These companies use low cost ingredients, large-scale production methods, and highly persuasive marketing to encourage widespread consumption.

With global annual sales reaching $1.9 trillion, UPFs represent the most profitable segment of the food industry. Manufacturers of these products have delivered more than half of the $2.9 trillion in shareholder payouts made by publicly listed food companies since 1962. The profits help fuel expansion, marketing power, and political influence, reinforcing corporate dominance over modern food systems.

The Series explains that UPF companies rely on sophisticated political strategies to protect their interests — blocking regulations, influencing scientific debates, shaping public opinion, supporting hundreds of interest groups, lobbying, donating to political campaigns, and engaging in litigation to delay policy action (paper 3, table 1 and figure 2).

Professor Simon Barquera, the National Institute of Public Health of Mexico, Mexico, states, “Powerful corporations — not individuals’ choices — are behind the global rise of ultra-processed foods. Through interest groups, these corporations often position themselves as part of the solution, but their actions tell a different story — one focused on protecting profits and resisting effective regulation.”

Urgent Need for a Unified Global Response

The authors call for a global public health movement to protect policy-making from industry interference, end ties between industry and health organizations, and strengthen networks advocating for reduced UPF consumption.

Professor Karen Hoffman, University of the Witwatersrand, South Africa, says, “Just as we confronted the tobacco industry decades ago, we need a bold, coordinated global response now to curb the overproportionate power of UPF corporations and build food systems that prioritize people’s health and well-being.”

They argue that transforming food systems requires a new vision that elevates local food producers, preserves cultural food traditions, promotes gender equity, and ensures that economic benefits flow to communities rather than to distant shareholders.

Dr. Phillip Baker concludes, “We are currently living in a world where our food options are increasingly dominated by UPFs, contributing to rising global levels of obesity, diabetes and mental ill-health. Our Series highlights that a different path is possible — one where governments regulate effectively, communities mobilize, and healthier diets are accessible and affordable for all.”

The Lancet Series on Ultra-Processed Foods and Human Health, was supported by funding from Bloomberg Philanthropies.

Without HSL, it would be reasonable to expect fat to build up, as though the body had lost access to its energy supply. Surprisingly, this is not what happens. Research involving both mice and patients with mutations in the HSL gene shows that the lack of this protein does not lead to excess fat or obesity. Instead, affected individuals experience a loss of fat mass, a condition known as lipodystrophy.

Although obesity and lipodystrophy appear to be complete opposites, both involve fat cells that do not function properly. As a result, each condition can contribute to metabolic disturbances and cardiovascular problems.

HSL Found in an Unexpected Location Inside Fat Cells

To understand this surprising behavior, a team led by Dominique Langin, professor at the University of Toulouse within the I2MC, took a closer look at where HSL is found inside adipocytes. The protein is well known for its role at the surface of lipid droplets, where it helps break down stored fat. However, the study revealed that HSL also resides inside the nucleus of fat cells. “In the nucleus of adipocytes, HSL is able to associate with many other proteins and take part in a program that maintains an optimal amount of adipose tissue and keeps adipocytes ‘healthy’,” explains Jérémy Dufau, co-author of the study, who completed his doctoral thesis on this topic.

The researchers also found that nuclear HSL levels are tightly controlled. Adrenaline, which activates the form of HSL located on lipid droplets, also encourages the protein to leave the nucleus. This process occurs naturally during fasting. In contrast, obese mice show elevated levels of HSL within the nucleus, suggesting a shift in this regulatory system.

A Revised Understanding of HSL’s Role in Metabolism

“HSL has been known since the 1960s as a fat-mobilizing enzyme. But we now know that it also plays an essential role in the nucleus of adipocytes, where it helps maintain healthy adipose tissue,” says Dominique Langin. This additional responsibility helps explain why the absence of HSL results in lipodystrophy, and it offers new insights into metabolic disorders such as obesity and related health complications.

This discovery appears at a critical time. In France, one in two adults is overweight or obese, and globally the number reaches two and a half billion people. Obesity increases the risk of a range of diseases, including diabetes and heart problems, and often reduces overall quality of life. Continued scientific research is crucial to improving prevention efforts and patient care.