The Problem
Obesity has become a worldwide epidemic.  Excess body fat is usually the first physical sign that your metabolism is disrupted and that your level of insulin resistance is rising, however about 16 percent of normal weight individuals have severe insulin resistance (1).  Not only is obesity a chronic inflammatory condition, but it also increases the production of senescent cells that drive the aging process (2). 

The physiological foundation of obesity is insulin resistance caused by decreased AMPK activity (3,4).  If AMPK activity is inhibited, the burning of excess body fat in every organ is compromised, and fat stores continue to increase.  However, that same inhibition of AMPK activity will also have negative consequences on your immune system, the ability to resolve inflammation, the expression of your genes, and the acceleration of aging.

The Traditional Medical Approach
The search for weight loss drugs has continued for nearly a century and has yet to generate sustainable results.  The current generation of injectable weight loss drugs stops hunger and reduces calorie intake, thus leading to weight loss.  Unfortunately, much of that weight loss comes from losing lean body mass (5).  This loss of lean body mass reduces the metabolic efficacy of every organ in the body.

The Metabolic Engineering™ Approach
Metabolic Engineering™ is a more comprehensive dietary technology to improve metabolic efficiency and repair damaged tissue by activating AMPK (6).  Increased AMPK activity also stimulates the oxidation of stored fat in every cell in the body. 

The goal of Metabolic Engineering™ is to activate AMPK in the adipose tissue.  Using the Zone diet component of Metabolic Engineering™ to restrict calories without hunger or fatigue is the most powerful dietary approach for increasing AMPK activity.  The omega-3 fatty acid dietary component of Metabolic Engineering™ reduces neuroinflammation and promotes its resolution.  The polyphenol dietary component of Metabolic Engineering™ reduces oxidative stress.  Equally important is that the omega-3 fatty acid and polyphenol components of Metabolic Engineering™ are also indirect activators of AMPK activity.   Thus, combining all three dietary interventions in Metabolic Engineering™ provides the optimal dietary approach to maximizing AMPK activity to metabolize stored excess body fat for energy. 

An added benefit of the benefit of following Metabolic Engineering™ to reduce excess body fat is that you will also reduce cellular senescence (7).   That is the true benefit of fat loss as it leads to a longer healthspan.

1. McLaughlin T, Allison G, Abbasi F, Lamendola C, Reaven G.Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals.  Metabolism. 2004; 53:495-9. doi: 10.1016/j.metabol.2003.10.032.

2. Burton DGA and Faragher RGA. Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing.  Biogerontology. 2018; 19(6): 447-459.doi: 10.1007/s10522-018-9763-7. 

3. Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome.  J Clin Invest. 2013; 123:2764-72. doi: 10.1172/JCI67227.

4. Saha AK, Xu XJ, Balon TW, Brandon A, Kraegen EW, Ruderman NB. Insulin resistance due to nutrient excess:  Is it a consequence of AMPK downregulation?Cell Cycle. 2011; 10: 3447-51. doi: 10.4161/cc.10.20.17886.

5. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group.Once-weekly semaglutide in adults with overweight or obesity.  N Engl J Med. 2021; 384: 989-1002. doi: 10.1056/NEJMoa2032183.

6. Sears B and Saha AK.Dietary control of inflammation and resolution. Front Nutr. 2021;8: 709435. doi: 10.3389/fnut.2021.709435.

7. List EO, Jensen E, Kowalski J, Buchman M, Berryman DE, Kopchick JJ. Diet-induced weight loss is sufficient to reduce senescent cell number in white adipose tissue of weight-cycled mice.  Nutr Healthy Aging.  2016 4:95-99. doi: 10.3233/NHA-1614.