Adipose tissue retains an epigenetic memory of obesity after weight loss

Adipose “Memory” and Cell Biology

• Several comments link the paper’s “obesogenic memory” to known facts: fat cells formed in adolescence largely persist, and adult weight gain mostly enlarges existing cells rather than creating new ones.
• Fat cells have ~10-year lifetimes; some argue a decade of good habits might mostly replace “obese” adipose cells, though it’s unclear how fully this erases epigenetic changes.
• Comparisons are made to “muscle memory”: skeletal muscle retains extra nuclei after growth, making regaining strength easier; fat tissue may analogously retain a pro-obesity bias.

Metabolism, CICO, and Insulin

• Strong debate over “calories in/calories out” (CICO):
  • One side insists thermodynamics ultimately governs weight; claims of maintaining or gaining weight on 200–1000 kcal/day are labeled implausible or due to misreporting.
  • Others counter that biology’s complexity (insulin resistance, NEAT downregulation, energy partitioning, water retention) makes simple CICO explanations inadequate in practice, even if physics isn’t violated.
• Insulin sensitivity is highlighted as critical: low sensitivity keeps the body longer in a fat-storing state; low-carb diets, fasting, and some supplements are said to improve it.

GLP‑1 Drugs and Chronic Management

• GLP‑1 agonists (semaglutide, tirzepatide) are widely discussed as a major advance: they reduce appetite and seem to help long-term weight control, though weight often returns when stopped.
• Some frame obesity as a chronic condition requiring ongoing management—via persistent lifestyle change or long-term GLP‑1 use—rather than a one-time “fix.”

Fasting, Keto, and Fat Adaptation

• “Fat adaptation” (greater reliance on fat oxidation, e.g., via low-carb/keto and endurance training) is generally viewed as real, not pure “bro science,” though its magnitude is debated.
• Extended fasting and intermittent fasting are reported to produce significant weight loss and possibly adipocyte apoptosis, but many find prolonged fasting unpleasant (sleep disturbance, constant hunger).

Diet, Satiety, and Yo‑Yo Patterns

• Consensus: sustainable habits beat short, extreme diets. Common tactics:
  • High protein and fiber, lower refined carbs and sugar (especially in drinks).
  • Emphasizing whole foods for satiety; some succeed with low-carb, others with plant‑based or carnivore.
  • Removing ultra‑palatable “junk” from the home environment.
• Yo‑yo dieting is described as common and psychologically damaging; some recommend cognitive‑behavioral therapy and daily weighing with journaling to manage behaviors and expectations.

Exercise and Muscle vs Fat

• Many stress resistance training to preserve/build muscle, improve hormones, and raise energy expenditure; cardio is seen as health-promoting but relatively weak for weight loss alone.
• Several note that prior periods of fitness make later re-training easier, paralleling discussions of adipose memory.