Browse the evidence

Macrophage-specific lipoprotein lipase (LPL) promotes atherosclerosis by acting as a bridging molecule for remnant lipoprotein uptake, leading to foam cell formation and plaque progression.

LPL helps clear fat from blood, but in immune cells within artery walls, it helps build plaques. Therapies targeting LPL must distinguish between clearing blood fat (good) and feeding artery plaques (bad).

Triple agonists targeting GLP-1, GIP, and Glucagon receptors improve energy expenditure and restore body weight in diet-induced obesity models more effectively than dual or mono-agonists.

Triple hormone agonists (GLP-1/GIP/Glucagon) are in development and show promise in animal studies for boosting energy expenditure and weight loss beyond what dual agonists achieve. They are not yet standard clinical care.

Semaglutide therapy in older adults with type 2 diabetes accelerates muscle mass loss and functional decline, with higher doses and lower baseline muscle mass predicting greater loss.

If you are taking Semaglutide and are over 65 with diabetes, monitor your muscle strength. The medication can cause muscle loss, especially at higher doses. To counter this, focus on resistance training and adequate protein intake, and discuss dose adjustments with your doctor if you notice weakness.

Unintentional weight loss in type 2 diabetes is associated with a higher risk of all-cause mortality, whereas the association with intentional weight loss is unclear.

Unintentional weight loss in type 2 diabetes should be taken seriously as it may signal underlying health issues and is linked to higher mortality. The impact of intentional weight loss on mortality is less clear, so patients should focus on overall health management rather than just weight loss.

The MAPK signaling pathway (specifically ERK, JNK, and p38) plays a complex, context-dependent role in obesity, regulating appetite, adipogenesis, and insulin resistance, with effects varying between in vitro and in vivo models.

Obesity involves complex signaling networks like MAPK that regulate fat storage and insulin sensitivity. The fact that these pathways have conflicting effects in different contexts explains why single-target interventions often fail and why obesity is a heterogeneous disorder.

A ketogenic diet reduces oxidative stress and improves mitochondrial function by activating antioxidant pathways (Nrf2) and scavenging reactive oxygen species (ROS) via ketone bodies like beta-hydroxybutyrate.

Adopting a ketogenic diet may help reduce cellular damage associated with aging and chronic disease by shifting your body's energy source to ketones, which appear to protect mitochondria and reduce oxidative stress.

Improvement in glycemic control in T2D patients leads to energy conservation via reduced glucosuria and osmotic water weight loss, which mechanically impedes scale-based weight reduction.

When you start treating your diabetes effectively, your blood sugar drops. This means your body stops peeing out calories (glucosuria) and starts storing water and glycogen again. You might see the scale go up by a few pounds. This is not fat gain; it is your body recovering from dehydration and energy loss. Do not stop your diabetes treatment because of this scale increase.

Adipose-specific overexpression of UCP1 via hADP promoter-modified plasmids induces thermogenesis and energy expenditure, leading to significant fat mass loss without lean mass loss in obese mice.

This research suggests that stimulating fat tissue to burn energy (thermogenesis) via a specific gene therapy could reduce fat mass without losing muscle. While promising in mice, this is not yet a human treatment. The key takeaway is that targeting energy expenditure in fat cells is a viable strategy for obesity, potentially avoiding the gut side effects of current drugs like GLP-1 agonists.

Intragastric balloons (IGBs) provide modest short-term weight loss (approx. 13% TBWL at 6 months) but are associated with higher adverse event rates and significant weight regain long-term, limiting their standalone efficacy.

IGBs can help you lose about 13% of your body weight in the first 6 months, but they are not a permanent solution. You will likely experience nausea and pain, and many people regain the weight after the balloon is removed. They are best used as a short-term tool to kickstart weight loss or as a bridge to surgery, combined with strict lifestyle changes.

Bariatric surgery may not provide long-term reductions in depressive symptoms for patients with obesity and depression, despite improving quality of life.

Bariatric surgery is effective for weight loss but may not resolve depression long-term. Ensure you have a mental health support plan before and after surgery.

Discontinuation of incretin therapy leads to weight regain that is proportional in composition (fat and lean mass) to the initial loss, challenging the belief that regained weight is predominantly fat.

If you stop your GLP-1 medication, you will likely regain weight. Contrary to popular belief, this regained weight is not just fat; it includes muscle and other lean tissue, following a similar ratio to what you lost. However, older adults may struggle to regenerate muscle, so maintaining activity is crucial.

Intentional weight loss induces physiological adaptations in energy expenditure and intake that actively oppose weight maintenance, contributing to weight regain.

If you have lost weight, expect your body to fight to regain it through increased hunger and lower energy burn. This is a biological adaptation, not a character flaw. Successful maintenance likely requires strategies that address these specific physiological drivers, such as managing hunger cues and adjusting activity levels, rather than relying on willpower alone.

Long-term maintenance of significant weight loss (>10%) following a Very Low Calorie Diet (VLCD) is rare, with only 5.9% of healthy participants sustaining loss after 15 years.

VLCD can help you lose weight quickly, but it is not a permanent fix. Without ongoing lifestyle changes, most people regain the weight within 15 years. Use it as a starting point, not a solution.

Greater weight loss achieved during VLCD is associated with a higher incidence of cardiovascular events in the 15 years following the intervention.

Losing a lot of weight quickly might not protect your heart in the long run if you regain it. Focus on steady, sustainable habits rather than extreme loss.

VLCD does not prevent the development of type 2 diabetes or impaired fasting glucose in the long term (15 years) for the majority of participants.

VLCD might put diabetes into remission for a short time, but it rarely prevents it long-term. You must maintain a healthy weight to keep blood sugar stable.

The mitochondrial uncoupler SHO1122147, administered at 200 mg/kg/day, significantly reduces body weight and liver triglycerides in a mouse model of MASH without causing hyperthermia or altering food intake.

This research identifies a specific compound (SHO1122147) that acts as a mitochondrial uncoupler to burn energy directly, leading to significant fat loss and improved liver health in a mouse model of fatty liver disease. Crucially, it achieved this without causing dangerous overheating or reducing the amount of food eaten. While not yet available for humans, it represents a potential future therapeutic class that targets energy expenditure rather than appetite, potentially avoiding the muscle loss and gastrointestinal side effects seen in current popular weight loss drugs.

Mild mitochondrial uncoupling promotes true ectopic lipid disposal by dissipating substrate energy as heat, thereby reducing lipid burden in non-adipose tissues without causing compensatory redistribution (the 'ballooning effect').

Current research suggests that 'mild' mitochondrial uncoupling is a promising therapeutic avenue for treating metabolic diseases like fatty liver and diabetes by burning off excess fat as heat. However, these are experimental pharmaceutical interventions (e.g., CRMP, BAM15) not yet available for general use. Natural methods like exercise and cold exposure also induce mild uncoupling and are the current safe way to leverage this mechanism.

Short-chain fatty acids (SCFAs) produced by gut bacteria have complex effects: while generally beneficial for blood pressure regulation via GPCR activation, increased production in obesity may contribute to calorie harvest and weight gain.

Fiber is good for your heart, but if you are struggling with weight, be aware that your gut bacteria might be extracting more calories from your food. Focus on a balanced diet rather than just maximizing fiber intake if weight loss is a primary goal.

Diet quality among U.S. adults improved modestly between 1999 and 2020.

Practitioners should note a modest improvement in diet quality over the past two decades.

The proportion of U.S. adults with poor diet quality remains high.

Practitioners should be aware that many adults still have poor diet quality.

Dietary disparities persist or are worsening among U.S. adults.

Practitioners should focus on addressing dietary disparities in their communities.

The proportion of new users of semaglutide (Ozempic ® ) with a record of type 2 diabetes (T2D) declined from 99% in 2018 to only 67% in 2022, before increasing again to 87% in 2023.

Practitioners should note the changing demographics of semaglutide users, indicating a shift towards off-label use.

Most initiators of semaglutide (Ozempic ® ) with T2D had suboptimal glucose control, with 83% having an HbA1c ≥ 48 mmol/mol.

Practitioners should be aware that many T2D patients starting semaglutide may not have optimal glucose control.

25.3% of plastic surgeons prescribed or utilized GLP-1 agonists in their practice.

A significant portion of plastic surgeons are incorporating GLP-1 agonists into their practice.