on June 25, 2026
Nutrition is not merely a means of taking in energy; it is one of the main determinants of human health throughout life. The way we eat influences energy metabolism, the endocrine system, the gut microbiota, immune function, cardiovascular health, the brain, and even the processes of biological aging.
Over recent decades, research has gradually moved beyond a purely calorie-based view of nutrition, recognizing that nutritional quality, meal composition, energy density, physical activity, and eating patterns interact in complex ways to regulate the body’s homeostasis.
The goal is not simply to maintain body weight, but to achieve metabolic health.
Energy expenditure: beyond simply counting calories
Total energy requirements are the sum of several physiological processes.
The largest share is accounted for by basal metabolic rate, that is, the energy required to maintain vital functions at rest: cardiac activity, breathing, maintenance of body temperature, neurological function, cell turnover, and liver and kidney activity.
Basal metabolic rate accounts for an average of 60–75% of daily energy expenditure, with variations related to:
age;
sex;
muscle mass;
hormonal status;
nutritional status;
ambient temperature;
pregnancy and breastfeeding;
medical conditions.
Additional components include:
diet-induced thermogenesis;
voluntary physical activity;
thermoregulation.
Diet-induced thermogenesis is the energy used to digest, absorb, and metabolize nutrients, and varies according to dietary composition: protein generally has the greatest thermogenic effect.
Studies show that diet quality and physical activity affect the risk of metabolic diseases far more than body weight alone.
A person of normal weight may have significant metabolic abnormalities, while physically active individuals often show better cardiometabolic markers, regardless of BMI.
Hunger and satiety: the ongoing dialogue between the gut, adipose tissue, and the brain
Appetite does not depend solely on willpower.
The regulation of hunger involves an extremely sophisticated neuroendocrine network.
The hypothalamus integrates signals from the:
gastrointestinal tract;
adipose tissue;
pancreas;
liver;
peripheral circulation;
autonomic nervous system.
Key biological mediators include:
Ghrelin
Produced mainly in the stomach.
It stimulates hunger and contributes to energy and neuroendocrine regulation.
Secretion increases before meals and decreases afterward.
Leptin
Produced by adipose tissue.
It sends the brain information about energy stores.
Under normal physiological conditions, it tends to reduce food intake and promote satiety.
Leptin resistance can develop in obesity.
Insulin
In addition to regulating blood glucose, it acts as a central metabolic signal.
Intestinal peptides
GLP-1, PYY, and CCK contribute to meal termination and the regulation of eating behavior.
When this system is disrupted by chronic stress, a highly processed diet, sedentary behavior, or endocrine disorders, hyperphagia, loss of appetite, or disordered eating may occur.
Plant-based nutrition, dietary diversity, and metabolic health
Current evidence supports a dietary pattern rich in minimally processed plant foods.
Vegetables, fruit, legumes, whole grains, oilseeds, nuts, herbs, and fermented foods provide:
fiber;
polyphenols;
carotenoids;
minerals;
vitamins;
bioactive compounds.
The protective effect comes not from a single food, but from variety.
The color of plant foods often reflects different phytochemical profiles:
red → lycopene, ellagitannins;
green → chlorophyll, folates;
orange → carotenoids;
blue-purple → anthocyanins.
Regular consumption of plant foods is associated with a lower risk of cardiovascular disease, type 2 diabetes, and all-cause mortality.
Physical activity: the primary regulator of metabolic health
Physical exercise is one of the most powerful non-pharmacological interventions.
Muscle activity:
increases insulin sensitivity;
improves mitochondrial function;
modulates inflammation;
reduces ectopic fat accumulation;
promotes cardiovascular health.
The benefits can be observed regardless of weight loss.
For this reason, the concept of “metabolic fitness” is now more useful than thinness alone.
International guidelines recommend at least:
150–300 minutes per week of moderate activity;
or 75–150 minutes of vigorous activity.
AMPK: the cellular energy sensor
One of the main metabolic regulators is AMP-activated protein kinase (AMPK).
This intracellular pathway is activated when energy availability declines.
Its effects include:
increased lipid oxidation;
improved insulin sensitivity;
stimulation of mitochondrial biogenesis;
modulation of autophagy.
Physical activity, moderate energy restriction, and a balanced diet can contribute to its activation.
The term “youth enzyme” is a popular simplification: AMPK is involved in the metabolic processes of aging, but it is not by itself an anti-aging mechanism.
Glycation, AGEs, and biological aging
Chronic excess glucose and metabolic dysfunction promote the formation of advanced glycation end products (AGEs).
AGEs can:
increase oxidative stress;
modify structural proteins;
promote chronic inflammation;
contribute to vascular damage.
They have been associated with the development of:
cardiovascular disease;
diabetic complications;
neurodegeneration;
accelerated aging.
Reducing ultra-processed foods, maintaining metabolic control, and leading an active lifestyle are useful ways to limit their accumulation.
Fasting, metabolic flexibility, and brain health
In recent years, interest in calorie restriction and time-restricted eating has grown.
During controlled periods of reduced energy availability, metabolic changes are observed:
reduced insulin levels;
lipid mobilization;
ketone body production.
Beta-hydroxybutyrate, the main ketone body, has biological effects on:
energy metabolism;
inflammation;
cell signaling.
Some studies suggest potential beneficial effects on metabolic function and neurological health.
However, fasting is not suitable for everyone and requires caution in:
pregnancy;
frail older adults;
eating disorders;
diabetes under treatment;
chronic diseases.
Autophagy, Exercise, and Biological Plasticity
Autophagy is a cellular process of intracellular recycling.
It is modulated by:
physical exercise;
energy status;
circadian rhythms.
This function contributes to the maintenance of cellular balance by eliminating damaged components.
Experimental studies show that regular physical activity and a proper nutritional balance promote metabolic adaptations associated with improved biological resilience.
Health does not depend on a single food, an extreme diet, or drastic practices.
It is the result of the continuous interaction between nutrition, movement, sleep, social relationships, the environment, and the body's ability to adapt.
Eating a varied diet, staying physically active, and respecting biological rhythms remain among the most solid and research-supported strategies for promoting health and longevity.
Essential Bibliography
Hall KD, et al. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain. Cell. 2019.
Morton GJ, Meek TH, Schwartz MW. Neurobiology of food intake in health and disease. Nat Rev Neurosci. 2014.
Friedman JM. Leptin and regulation of body weight. Nature. 1998.
Hardie DG. AMPK: a key regulator of energy balance. Nat Rev Mol Cell Biol. 2012.
Longo VD, Mattson MP. Fasting: Molecular Mechanisms and Clinical Applications. Cell Metabolism. 2014.
de Cabo R, Mattson MP. Effects of Intermittent Fasting on Health and Aging. NEJM. 2019.
Lopez-Otin C, et al. The Hallmarks of Aging. Cell. 2013.
Warburton DER, Bredin SSD. Health benefits of physical activity. CMAJ. 2017.
Mattson MP. Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metabolism. 2012.
Levine ME, et al. Low protein intake and reduced IGF-1 signaling. Cell Metabolism. 2014.
