OBESITY AND METABOLIC SYNDROME: PANDEMIC OF THE 21TH CENTURY

Giugno 26, 2024

Obesity is a chronic (long-standing), relapsing disease characterized by an excess of adipose tissue mass. Although the body mass index (BMI) method is not very accurate as it does not account for muscle mass, the World Health Organization still classifies obesity using BMI due to its ease of use, and this classification is widely used in practice. According to the World Obesity Atlas [1], the prevalence of obesity in the European region is expected to rise, affecting 35% of all women and 39% of all men by 2035.

Can obese individuals be metabolically healthy, and what does this mean? The answer is no. “Metabolically healthy” obese individuals have increased levels of subcutaneous white adipose tissue without excessive intra-abdominal fat deposits in organs such as the liver, skeletal muscles, heart, and pancreas. They exhibit reduced markers of systemic inflammation but have increased levels of leptin and resistin [2]. Leptin, a satiety hormone, when overproduced, leads to insensitivity in the hypothalamus and delayed satiety. Resistin is associated with insulin resistance, a risk factor for developing metabolic syndrome, prediabetes, and diabetes. Another important hormone involved in obesity development is ghrelin, known as hunger hormone, which is involved in appetite regulation. It was shown that obese individuals have altered ghrelin levels [3].

While metabolically healthy obesity is not associated with increased short-term risk of type 2 diabetes and cardiovascular disease, it still significantly increases the long-term risk: a 49% increased risk of coronary heart disease, a 7% increased risk of cerebrovascular disease, and a 96% increased risk of heart failure compared to normal-weight population without metabolic abnormalities [4].

Another common risk factor for cardiovascular disease and type 2 diabetes is metabolic syndrome. Subjects with metabolic syndrome can have normal body mass index, but have increased fat mass in the abdomen, around the organs in even within them (the so-called visceral fat, for example, fat infiltration in the liver). Metabolic syndrome is a combination of various symptoms diagnosed by health professionals, requiring at least three of the following criteria to be met [5]:

  • Central or abdominal obesity (waist circumference ≥80 cm in females and ≥94 cm in males)
  • High triglyceride levels in the blood (>1.7 mmol/L or ≥150mg/dL or receiving dyslipidemia treatment);
  • Reduced high-density lipoprotein levels (<1.3 mmol/L or <50 mg/dL in females and <1.0 mmol/L or <40 mg/dL in males or receiving dyslipidemia treatment);
  • Elevated blood pressure (systolic ≥130 mmHg and/or diastolic ≥85 mmHg or taking antihypertensive medication);
  • Elevated fasting glucose levels (glycemia ≥5.6 mmol/L or ≥100 mg/dL or receiving glucose-lowering treatment).

Subjects with metabolic syndrome have increased risk for myocardial infarction, stroke and peripheral vascular disease, type 2 diabetes, and predisposition to neurodegenerative dysfunction, for instance, Alzheimer’s disease etc.

Both obesity and metabolic syndrome are preventable, with weight reduction being one of the key components. A modest weight loss of 1 – 5% of total body weight can normalize blood pressure and glycemia. Greater weight loss, such as 5 – 10%, can further enhance health by reducing adipocyte accumulation in the liver [6].

Calorie balance is the cornerstone of weight reduction, with one side of the scale representing calories consumed through food intake and the other side representing calories expended through physical activity.

The nervous system and hormonal interactions determine food intake and energy expenditure. For example, homeostatic eating is controlled by the hypothalamus, a tiny brain structure, where the satiety center is located. In individuals with normal weight, satiety hormones (like glucagon-like peptide-1, oxyntomodulin, leptin, and peptide YY etc.) signal fullness after about 20 minutes. However, in overweight individuals this signalling occurs approximately after 30 minutes. Consequently, eating faster leads to higher calorie consumption [7].

The mesolimbic system is responsible for hedonic eating – consuming food for pleasure rather than energy homeostasis. It activates reward circuits with dopamine, opiates, and endocannabinoids, stimulating persistent hunger and inhibiting satiety [8,9]. To counteract this, practice mindful eating, recognize true hunger cues, and strengthen the prefrontal cortex, which governs executive function and self-regulation [6,7]. Using cognitive-behavioural strategies can enhance self-control and reduce hedonic eating impulses. Additionally, finding enjoyable activities unrelated to food can help shift the focus away from eating for pleasure.

By Jelizaveta Sokolowska, Zane Šmite, Sabine Skrebinska and all the Laboratory for Personalized Medicine at the Department of Internal Medicine Latvia University Team

References:

[1] World Obesity Federation, World Obesity Atlas 2023. Available at https://data.worldobesity.org/ publications/?cat=19

[2] Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020 Feb 25;7:22. doi: 10.3389/fcvm.2020.00022. PMID: 32158768

[3] Wang Y, Wu Q, Zhou Q, Chen Y, Lei X, Chen Y, Chen Q. Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis. Sci Rep. 2022 Feb 17;12(1):2679. doi: 10.1038/s41598-022-06636-3. PMID: 35177705; PMCID: PMC8854418.

[4] Caleyachetty R, et al. Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. J Am Coll Cardiol. 2017 Sep 19;70(12):1429-1437. doi: 10.1016/j.jacc.2017.07.763. PMID: 28911506.

[5] Alberti KG, et al. Circulation. 2009 Oct 20, 120 (16):1640-5.

[6] Horn DB, et al. What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review. Postgrad Med. 2022 May;134(4):359-375. doi: 10.1080/00325481.2022.2051366. Epub 2022 Apr 26. PMID: 35315311.

[7] Yeung AY, Tadi P. Physiology, Obesity Neurohormonal Appetite And Satiety Control. 2023 Jan 3. In: StatPearls [Internet]. PMID: 32310366.

[8] Theilade S, et al. An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight. Diabetes Obes Metab. 2021 Feb;23 Suppl 1:17-35. doi: 10.1111/dom.14270. PMID: 33621414.

[9] Heni M, et al. Impaired insulin action in the human brain: causes and metabolic consequences. Nat Rev Endocrinol. 2015 Dec;11(12):701-11. doi: 10.1038/nrendo.2015.173. Epub 2015 Oct 13. PMID: 26460339.