Browse the evidence

Abdominal obesity is a significant risk factor for endometrial cancer, with risk increasing in a dose-dependent manner with weight gain, largely mediated by 'unopposed estrogen' from increased bioavailable oestrogens and low progesterone.

Maintaining a healthy weight is one of the most effective ways to reduce endometrial cancer risk. This risk is driven by hormonal imbalances, specifically high oestrogen and low progesterone. Weight loss, especially reducing abdominal fat, can significantly lower this risk.

Obesity increases the risk of oesophageal adenocarcinoma, primarily through gastroesophageal reflux and oesophagitis, whereas it may have an inverse or neutral association with oesophageal squamous cell carcinoma.

If you are obese, you are at higher risk for oesophageal adenocarcinoma, largely due to increased reflux. Managing your weight can reduce reflux and this risk. Be aware of chronic heartburn and seek medical advice if it persists.

Mitochondrial dysfunction is a necessary driver of the Senescence-Associated Secretory Phenotype (SASP), as evidenced by the elimination of SASP in cells devoid of mitochondria, while irreversible cell cycle arrest persists.

Aging and age-related inflammation are driven by dysfunctional mitochondria producing the SASP. Interventions that target mitochondrial health (e.g., senolytics, senostatics like rapamycin or metformin) may reduce this inflammatory burden. Focus on strategies that support mitochondrial quality control, such as exercise and metabolic health, rather than just energy output.

Exogenous ghrelin infusion suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans in a dose-dependent manner.

This research indicates that higher levels of the hormone ghrelin directly reduce the body's ability to secrete insulin in response to glucose, leading to worse glucose tolerance. For healthy individuals, this suggests that conditions or interventions that significantly elevate ghrelin (like prolonged fasting or specific pharmacological agents) might impair glucose handling. It does not suggest using ghrelin as a treatment, but rather highlights it as a factor to consider in metabolic health.

Loss of Bardet-Biedl syndrome (BBS) proteins causes leptin resistance and obesity by disrupting the physical interaction between BBS1 and the leptin receptor (LepRb), leading to defective intracellular trafficking and attenuated hypothalamic signaling.

This research identifies a specific biological mechanism where genetic defects prevent the brain from properly processing the 'fullness' signal (leptin) from fat cells. For individuals with Bardet-Biedl Syndrome or similar genetic variants affecting ciliary function, standard weight loss advice may fail because the body's internal signaling hardware is broken, not just the caloric balance. Future treatments may need to target the trafficking of the leptin receptor itself rather than just focusing on calorie intake.

Following an oral glucose load, skeletal muscle oxidation is the predominant metabolic fate of the glucose taken up by muscle, whereas glycogen storage accounts for less than 10% of the total oral load.

When you eat carbohydrates, your muscles primarily burn them for energy (oxidation) rather than storing them as glycogen. Only a small fraction (<10% of the total load) is stored in muscle. This challenges the common assumption that muscle is the main storage site for post-meal glucose.

Cognitive engagement and mental stimulation build 'brain and cognitive reserve,' which delays the clinical manifestation of dementia and cognitive decline by increasing neural efficiency and structural resilience.

Actively engage in mentally stimulating activities such as learning a new language, playing musical instruments, solving puzzles, or participating in discussion groups. These activities build cognitive reserve, which helps delay the onset of dementia symptoms.

PPARg is the master regulator of adipocyte differentiation; its deletion prevents fat cell development, while its activation is sufficient to induce adipogenesis in non-adipocyte cell types.

PPARg is the genetic switch for fat cell creation. Drugs like thiazolidinediones target this receptor to treat diabetes, highlighting its central role in metabolic health and fat storage.

Obstructive sleep apnoea (OSA) contributes to the development of insulin resistance and elevated inflammatory cytokines (IL-6, TNF-alpha) independently of obesity, with visceral fat being the primary anatomical driver.

If you have sleep apnoea, treating the breathing obstruction (e.g., with CPAP) is important, but it does not automatically fix your metabolic health. You must actively manage insulin sensitivity through diet and exercise, as OSA independently drives inflammation and insulin resistance regardless of your weight.

Metabolic syndrome (MetS) is independently associated with a higher risk of major cardiovascular events, cardiovascular mortality, and all-cause mortality, advancing the onset of these risks by approximately 3.2 years.

Having metabolic syndrome significantly increases your risk of heart attack, stroke, and early death, advancing the onset of these risks by over 3 years. However, managing individual components like high blood pressure, high triglycerides, or low HDL cholesterol is just as effective for risk reduction as treating the syndrome as a whole unit. Focus on controlling these specific metrics.

Metabolic syndrome is NOT associated with a higher risk of myocardial infarction or stroke, although individual components like elevated blood pressure, reduced HDL, and elevated triglycerides are.

Having metabolic syndrome does not necessarily increase your risk of heart attack or stroke, but managing individual components like high blood pressure, low HDL cholesterol, and high triglycerides does reduce this risk. Focus on controlling these specific markers.

Elevated tissue levels of specific ceramide species (C16:0 and C18:0) directly cause insulin resistance and metabolic dysfunction by inhibiting Akt/PKB signaling and mitochondrial efficiency.

High levels of specific fats called ceramides (C16:0 and C18:0) block your body's ability to use insulin, leading to high blood sugar and metabolic disease. While not all fats are bad, these specific ones are key drivers of insulin resistance. Managing overall metabolic health involves addressing these specific lipid accumulations, often through lifestyle changes that improve insulin sensitivity.

Perilipin phosphorylation by PKA is not required for Hormone-sensitive Lipase (HSL) translocation to lipid droplets, but is strictly required for the lipolytic activity of HSL once it is associated with the lipid droplet.

This research clarifies that the body's fat-burning machinery (HSL) can physically reach fat stores without the specific hormonal 'permission' (phosphorylation) previously thought necessary. However, without that hormonal signal, the fat is not actually broken down. This implies that while the machinery is present, the actual release of fatty acids depends on the hormonal state (e.g., stress, fasting, exercise) triggering the final catalytic step, not just the movement of the enzyme.

Carbohydrate loading (supercompensation) provides no performance benefit for trained runners during a 20.9-km run, as performance times were statistically identical regardless of initial muscle glycogen levels.

For a 13-mile run, you do not need to perform extreme carbohydrate loading (like eating 500+ grams of carbs for 3 days). Your performance will be the same whether you have 'supercompensated' glycogen or normal levels. Focus on maintaining adequate daily carbohydrate intake rather than trying to maximize stores through extreme diets.

Higher initial muscle glycogen levels lead to a greater rate of glycogen utilization during exercise, but this does not improve performance in a 20.9-km run.

If you have high glycogen, your body will burn more of it during your run compared to if you have low glycogen. However, for a 13-mile run, this extra burn doesn't make you faster. Don't stress about maximizing glycogen.

Colonic SCFA mixtures attenuate whole-body lipolysis, indicated by decreased fasting free glycerol concentrations.

SCFAs may help reduce the release of fatty acids from fat cells (lipolysis). While this might sound counterintuitive for weight loss, it can help prevent fat from accumulating in the liver and muscles, improving insulin sensitivity. Focus on fiber intake to support this process.

Prolonged TNF-α antagonism via etanercept improves fasting glucose and increases the proportion of high molecular weight (HMW) adiponectin in obese subjects with metabolic syndrome.

For obese individuals with metabolic syndrome, blocking TNF-α using etanercept can lower fasting glucose and improve the beneficial ratio of high molecular weight adiponectin. This is not a standard weight-loss treatment due to infection risks, but it may be a beneficial side effect for patients already treating autoimmune diseases like rheumatoid arthritis.

TNF-α antagonism with etanercept increases the ratio of high molecular weight (HMW) adiponectin to total adiponectin without changing total adiponectin levels or body composition.

Etanercept improves metabolic health by shifting adiponectin toward its most active form (HMW), rather than just increasing total amounts. This suggests TNF-α blockade helps the body utilize existing adiponectin more effectively.

Body fatness is regulated by an active biological feedback system (set point) involving signals like leptin that defend a target level of adiposity by modulating intake and expenditure.

Understand that your body has a biological 'thermostat' for fat. When you lose weight, your body actively fights to regain it by increasing hunger and decreasing energy expenditure. This is a normal biological response, not a personal failure. Successful long-term management requires strategies that account for this biological resistance, such as gradual changes and focusing on sustainable habits rather than rapid loss.

Body weight and adiposity settle at a level determined by environmental factors (intake) and passive physical constraints (expenditure proportional to mass), without an active defended set point.

Your weight settles where your environment allows it to. If you live in an environment with high-calorie food and low physical activity, your weight will settle higher. To change your weight, you must change the environmental inputs (food availability, portion sizes) and outputs (physical activity), as your body passively adjusts expenditure to match the new mass.

Chronological age induces significant, tissue-specific changes in gene expression in human skin and adipose tissue, but not in lymphoblastoid cell lines (LCLs) or fresh lymphocytes, with minimal overlap of age-regulated genes across these tissues.

Aging affects gene expression differently in different tissues. You cannot assume that a blood test or a skin cream will have the same molecular impact on your brain or fat. Effective anti-aging strategies may need to be tissue-specific, as the molecular drivers of aging in skin (e.g., collagen, metabolism) differ from those in adipose or brain tissue.

Gastric bypass surgery increases postprandial PYY levels, which contributes to reduced food intake and weight loss.

Bariatric surgery works partly by changing how your gut hormones signal fullness. After surgery, your body releases more PYY, which helps you feel full faster and stay full longer, contributing to sustained weight loss beyond just having a smaller stomach.

Serotonin 2C receptors (5-HT2CRs) expressed by POMC neurons mediate the anorexigenic effects of serotonin and drugs like lorcaserin.

Drugs like lorcaserin work by targeting serotonin receptors on specific brain neurons to reduce appetite.

Heme oxygenase-1 (HO-1) promotes early muscle regeneration by enhancing myoblast proliferation and reducing mortality, but its temporal regulation is critical; sustained HO-1 expression inhibits terminal differentiation by blocking MyoD and myogenin.

HO-1 is a key enzyme that helps muscle stem cells multiply after injury, but it must be turned off later to allow muscles to fully mature. Artificially maintaining high HO-1 levels might stop muscles from finishing their repair process. Focus on natural recovery processes rather than trying to sustain high levels of specific enzymes indefinitely.