A New Lens on Metabolism
Metabolism is typically understood as the body's engine - a set of chemical reactions that generate and manage energy. But from a clinical psychoneuroimmunology (CPNI) perspective, metabolism is not merely a biochemical process but an integrative response system - a real-time reflection of how the body perceives, processes, and adapts to both its internal state and external environment.
Looking through this lens challenges us to see metabolism not only as the management of fuel and waste but as a neuro-immuno-endocrine interface - constantly shaped by signals of safety, threat, immune activity, hormonal rhythms, and even emotional memory. When metabolism becomes dysregulated, it may not be a sign of dysfunction in isolation, but rather the body’s appropriate response to inappropriate or unresolved circumstances.
In this blog, we will explore metabolism from a CPNI viewpoint - one that connects stress physiology, thyroid signalling, immune activation, interoception, and trauma. For health professionals, this integrated view opens the door to more compassionate, accurate, and effective care strategies for metabolic dysregulation.
Metabolism as an Adaptive Communication System
Under homeostatic conditions, the body manages energy through a delicate integration of nervous, hormonal, and immune signals. The hypothalamus plays a central role, receiving input from the periphery about energy availability, temperature, circadian timing, immune activation, and more. It orchestrates downstream hormonal cascades, including those involving insulin, thyroid hormones, noradrenaline and cortisol to ensure appropriate energy distribution.
But metabolism is not merely responsive, it is predictive. The brain continuously anticipates future energy needs based on learned patterns and contextual cues. If the environment is perceived as safe, metabolism can afford to be flexible, supporting digestion, repair, reproduction, and cognitive function. But if the body perceives a threat - whether physical, emotional, social, or immune - energy priorities shift immediately. In these moments, the system reallocates energy to fuel short-term survival.
This shift in priority is mediated by the stress system, both the Sympatho-Adreno-Medullary (SAM) axis and the Hypothalamic-Pituitary-Adrenal (HPA) axis, which become central to understanding how metabolism adapts under threat.
The Stress System and Metabolic Trade-Offs
When the brain detects a real or perceived danger, the locus coeruleus - a brainstem nucleus, is activated. The locus coeruleus increases noradrenaline output in the brain, enhancing alertness and vigilance. It simultaneously stimulates the sympathetic nervous system activating the adrenal medulla (SAM-axis) which releases adrenaline and noradrenaline.
In parallel, the locus coeruleus activates the HPA axis The hypothalamus secretes corticotropin- releasing hormone (CRH), which stimulates the release of adrenocorticotropic hormone (ACTH) from the pituitary gland. ACTH then signals the adrenal cortex to produce cortisol, the primary glucocorticoid involved in stress responses.
Thyroid Function and Context-Sensitive Metabolic Modulation
Thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3), are central regulators of metabolic rate, influencing nearly every tissue in the body. They increase mitochondrial activity, promote oxygen consumption, and support lipid and carbohydrate metabolism. Yet, their function is highly modulated by internal context particularly stress, inflammation, and perceived safety.
During acute or chronic stress, the body suppresses thyroid axis signalling in several ways. The hypothalamus reduces production of thyrotropin-releasing hormone (TRH), the pituitary lowers thyroid-stimulating hormone (TSH) output, and peripheral tissues decrease the conversion of T4 to active T3, instead producing reverse T3, an inactive form that acts as a brake on metabolic activity.
Cytokines released during immune activation, including IL-1β, IL-6, and TNF-α, can further impair thyroid hormone production and signalling, creating a localised or systemic hypothyroid state. This response is well-documented in the context of infection or trauma, where it serves to conserve energy. But when prolonged, it contributes to symptoms such as fatigue, depression, cold intolerance, and metabolic rigidity.
Clinically, this means that many individuals may present with thyroid-related symptoms despite normal TSH levels. Standard testing may not reveal low T3 or elevated reverse T3, and the root cause, often chronic inflammation or stress, remains unaddressed. Understanding thyroid function in context allows practitioners to move beyond a narrow interpretation of labs and toward a more nuanced approach.
Immune Activation and Metabolic Reprogramming
The immune system is one of the most energy-demanding systems in the body. During an immune response, metabolic resources are redirected to support the synthesis of cytokines, the proliferation of immune cells, and the generation of fever. This is managed by a process called “immune- metabolic reprogramming,” which prioritises survival during infection or injury.
When cytokines like IL-6 and TNF-α are released, they alter how cells use energy. Insulin resistance is induced to ensure that glucose remains available for immune cells, which rely on aerobic glycolysis during activation. Appetite suppression, fatigue, and social withdrawal - features of sickness behaviour - are orchestrated by the brain in response to cytokine signalling, reinforcing rest and energy conservation.
This process is beneficial in the short term. But in conditions of low-grade chronic inflammation such as we see in obesity, autoimmune disease, metabolic syndrome, or unresolved trauma, these same processes contribute to long-term metabolic dysfunction. Insulin resistance become entrenched, mitochondrial function deteriorates, and the body loses its ability to shift flexibly between fuel sources. This is not a random breakdown of metabolic regulation, it is a chronic immune prioritisation state, a body stuck in defensive mode, allocating resources as if an infection was ongoing. Healing requires downregulating this immune vigilance, restoring anti-inflammatory tone, and reintroducing metabolic flexibility.
The Role of Interoception and Vagal Signalling in Metabolic Health
One of the most overlooked yet critical aspects of metabolism is interoception or the ability to perceive internal bodily signals such as hunger, fullness, energy levels, and emotional states. Interoceptive awareness is mediated in large part by the Vagus nerve, which sends continuous feedback from the gut, heart, lungs, and immune system to the brain.
When vagal tone is high that is, when parasympathetic activity is robust, individuals are more able to feel internal cues accurately. They sense satiety, modulate their breathing in response to stress, and maintain autonomic flexibility. However, in chronic stress or trauma, vagal tone is suppressed, and interoceptive signals become blunted or distorted. This leads to a disconnect between physiological needs and behavioural responses. Individuals may overeat without feeling full, ignore hunger cues, or fail to register fatigue. Clinically, restoring interoceptive awareness is essential for re-regulating metabolism. Somatic therapies, breathwork, mindfulness, and safe therapeutic relationships can all enhance vagal tone and re-establish body awareness.
Living in a Metabolic Posture of Defence
In modern society, many individuals live in a chronic state of low-grade or non-survival threat. This may be due to psychological stress, environmental toxins, sleep disruption, processed foods, social disconnection, or unresolved trauma. Over time, the body settles into what might be called a metabolic posture of defence.
In this state, the HPA axis remains overactive, the thyroid is downregulated, insulin resistance becomes normalised, and the immune system continues to send low-level alarm signals. Even bone joins the conversation: recent findings on osteocalcin, a hormone secreted by bone under stress, suggest it plays a role in regulating glucose metabolism, immune activity and even cognition - further evidence that metabolism is a whole-body, whole-context phenomenon. Everything is everywhere all at the same time.
Clinically, this means that common metabolic complaints such as fatigue, stubborn weight gain, brain fog, digestive dysfunction are not just biochemical imbalances, but adaptive physiological strategies playing out in the wrong context. These bodies are doing what they were designed to do - survive danger - but the danger has never passed.
Clinical Reflections: Working with Metabolism as a Narrative
For health professionals, this clinical psychoneuroimmunological view of metabolism invites a radical shift in approach. Rather than managing metabolism as a mechanical output problem, we can engage with it as a narrative system, one that reflects a person’s lived experience, biology, and story of safety or threat.
This might involve reframing metabolic disorders not as failures of will or broken organs, but as intelligent adjustments to life circumstances. It means listening for the story behind the symptoms, the early adversity, the unresolved inflammation, the state of the autonomic nervous system.
It also means prioritising the restoration of safety as a therapeutic goal. Before asking the body to shed weight, regulate insulin, or enhance performance, we may need to guide it out of defence and into regeneration. Techniques such as nervous system regulation, somatic therapy, trauma-informed coaching, and restorative nutrition and sleep can all help return the body to a state where it can finally trust enough to heal.
Bringing Testing into Context: The Clinical Value of Metabolic and Inflammatory Markers
Within this framework, biochemical testing serves not only as a diagnostic tool but also as a window into the body's adaptive priorities. Conventional markers, when viewed in isolation, may miss the broader picture of stress physiology and immune-metabolic adaptation. However, when interpreted within the context of perceived safety/threat, chronic inflammation, and neuroendocrine signalling, they become powerful indicators of systemic load.
Fasting insulin, for instance, can reveal early insulin resistance long before glucose or HbA1c levels shift, offering a sensitive measure of the body's current metabolic demands and its capacity to respond. Elevated insulin in a euglycaemic individual may reflect a persistent drive to store energy, a signature of defensive physiology.
HbA1c and fasting glucose provide good insight into longer-term glycaemic control and are important markers to include when assessing metabolic health. Note however in the context of chronic stress or inflammation, HbA1c and fasting glucose might show normal levels even though there are ongoing metabolic disruptions, like early insulin resistance or shifts in triglycerides. In such cases, HbA1c and fasting glucose may not capture the subtler, earlier changes in metabolism.
Uric acid, traditionally associated with gout, has emerged as a metabolic danger signal, linked to fructose metabolism, mitochondrial stress, and immune activation. Elevated levels may indicate oxidative burden and impaired metabolic flexibility.
Cholesterol and triglycerides carry more meaning when interpreted through the lens of stress physiology. For example, elevated triglycerides may reflect liver insulin resistance, while altered HDL or LDL patterns may signify shifts in lipid transport under inflammatory load.
Importantly, interleukin-1 (IL-1β) and interleukin-6 (IL-6) while not routinely tested in primary care are invaluable in specialised practice. These cytokines reflect the inflammatory tone of the immune system and are key orchestrators of the immune-metabolic response. Their presence often explains symptoms and metabolic dysfunction in clients who appear “within range” by conventional markers but remain clinically unwell.
Together, these markers offer not just data points, but a narrative of how the body is attempting to survive and self-regulate. They help practitioners distinguish between metabolic dysfunction due to poor input and dysfunction rooted in unresolved defence physiology - guiding more precise, compassionate, and effective interventions.
Check out our MAP-series or metabolic assessment panels – developed to help you evaluate your client’s metabolic picture. https://www.colabeu.com/our-tests-non-members/#map-series
See also our LM4511 Thyroid Panel with Thyroglobulin Antibodies and Reverse T3
In summary: Reclaiming Metabolic Flexibility Through Safety
Metabolism is not just what we eat or how much we move. It is the sum expression of how safe we feel, how inflamed we are, how well we repair, and how deeply we connect to our own body signals. When viewed through the lens of psychoneuroimmunology, metabolic dysfunction becomes an invitation to listen, to regulate, and to restore.