Mixed
Prevention and reversal of the transition from metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO) requires multifaceted interventions targeting both adipose tissue intrinsic factors (e.g., promoting adipogenesis) and extrinsic drivers (e.g., hyperinsulinemia, circadian disruption), with lifestyle changes serving as the foundation but often requiring pharmacological or surgical augmentation for substantial weight loss and metabolic correction.
If you have obesity but normal metabolic markers (MHO), do not assume you are safe. Approximately half of people in this category will develop metabolic complications (MUO) over time. Focus on lifestyle changes (diet, exercise) to maintain metabolic health. If lifestyle changes are insufficient to prevent progression, consult a healthcare provider about pharmacological or surgical options to address underlying drivers like hyperinsulinemia or adipose dysfunction.
Thus, understanding the molecular determinants of this transition becomes critical with the potential to also lead into precision medicine approaches. ... approaches/therapies to prevent or reverse progression from MHO to MUO may need to be multifaceted, with focus on direct modification of adipose tissue as well as on factors extrinsic to adipose tissue (Figure 3). ... lifestyle changes alone will be insufficient for many, such that combination with drugs that directly reverse metabolic abnormalities of MUO and/or promote substantial weight loss, or bariatric surgery is likely to be also required.
Why this rating
The paper is a review summarizing multiple observational and interventional studies, providing strong mechanistic and clinical evidence, though not a single primary RCT.
Source
Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity
Tenzin Dagpo et al. · Cells · 2020
DOI 10.3390/cells9071596
More from this paper
- Hyperinsulinemia acts as an upstream driver of the transition from MHO to MUO by promoting excessive fat accumulation and insulin resistance, and therapies that suppress insulin secretion (e.g., diazoxide, octreotide) may prevent this progression.Good
- Promoting adipogenesis (the creation of new, functional adipocytes) through therapeutic agents can improve lipid storage capacity and prevent the transition from MHO to MUO by avoiding adipocyte dysfunction, hypoxia, and inflammation.Moderate
Related findings · Mixed
- Bariatric surgery (VSG and RYGB) is the most effective and sustainable treatment for obesity, producing marked and sustained weight loss that non-surgical interventions cannot match.Strong
- Severely protein-deficient diets (2–3% energy) induce lean body mass loss and metabolic imbalance, whereas adequate protein intake (0.66 g/kg/d minimum) is a prerequisite for maintaining muscle, bone, and physiological function.Strong
- For patients with Class III obesity (BMI >39.9 kg/m2), metabolic bariatric surgery (MBS) is significantly more effective than any currently approved medication, with BilioPancreatic Diversion (BPD) showing the highest estimated weight loss.Strong
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