Causes and solutions to “globesity”: The new fa(s)t alarming global epidemic

Highlights

• Obesity pathology, risk factors and complications.

• Current anti-obesity treatment options.

• Novel targets in obesity research.

• Medicinal plants and plant-derived compounds with anti-obesity potential.

• Evaluation of efficacy and toxicity data from in vitro, iv vivo and clinical studies.

Abstract

Diverse groups of factors are leading to increased weight gain and obesity, such as certain genetic phenotypes, neuroendocrine disturbances, the administration of some drugs, behavioral, social and environmental factors. The progressively escalating rates of overweight and obesity worldwide have led to an introduction of a new term “globesity”. Excessive accumulation of body fat and especially of visceral adipose tissue is the main predisposing factor for the development of metabolic syndrome and other obesity related co-morbidities. At the present moment only few pharmacotherapeuticals are used for long-term treatment of obesity acting on narrow target spectra, e.g. pancreatic and gastric lipase inhibition, acting as adrenomimetics or activating the satiety centers in hypothalamus. Plant-based medications that accelerate weight loss, proved to be safe, effective and widely available, would be a preferable alternative for anti-obesity treatments. As plant extracts are multi-component systems they could also act by more than one mechanism, including decreased lipid absorption, decreased energy intake, increased energy expenditure, decreased pre-adipocyte differentiation and proliferation, decreased lipogenesis and increased lipolysis.

The current review gives a summary of the risk factors for obesity development and its characteristics consequences. Current treatment options, combining lifestyle changes and conventional treatment with commercial anti-obesity drugs have been described as well. Special emphasis on in vitro, in vivo and human studies, of potential medicinal plant extracts and phytochemicals, such as polyphenols, terpenoids, alkaloids, saponins, able to modulate the molecular pathways and gene/protein expressions related to obesity, have been highlighted.

Introduction

The number of people out of normal body weight range is constantly growing worldwide, indicating overweight and obesity as global concerns with expanding distribution. In 2016, more than 1.9 billion people, over 18 years, have been defined as overweight and above 0.65 billion of them as obese (NCD Risk Factor Collaboration, 2017). The worldwide prevalence of obesity expanded about three times within last ca. 40 years (between 1975 and 2016), defining obesity as global epidemics, hence introducing the term “globesity” (WHO, 2017).

The view of obesity as an imbalance between calories consumed and energy expended is nowadays rather oversimplified, since its multiplex etiology (González-Muniesa et al., 2017), comprising diverse groups of risk factors, such as certain genetic phenotypes [mutation in the leptin gene, fat mass and obesity associated (FTO) gene, melanocortin 4 receptor (MC4R) gene, etc.], neuroendocrine disturbances (hypothyroidism, hypogonadism, Cushing disease, etc.), behavioral factors (excessive consumption of “fast food” products, alcohol misuse), environmental factors (urbanization and pollution), epigenetic changes (Cheng et al., 2018) and some classes of obesogenic drugs (antidepressants, antiepileptics or antipsychotics) (Ghosh and Bouchard, 2017; Karam and McFarlane, 2007).

Obesity could be defined as a multifactorial disease characterized by excess adipose biomass (hypertrophy) and adipose tissue expansion (hyperplasia; Wang et al., 2014a, Wang et al., 2014b), associated with co-morbid metabolic and chronic diseases, including low-grade inflammation, metabolic syndrome (MetS) (González-Muniesa et al., 2017), type 2 diabetes, elevated blood glucose, insulin resistance (Sompong et al., 2016), cardiovascular diseases, hypertension, dyslipidemia, polycystic ovary syndrome (Hosseinkhani et al., 2018) and carcinogenesis (e.g. breast, colon, pancreas, kidney, esophagus, liver and prostate cancer; Wyatt et al., 2015). Social isolation, low self-esteem and chronic stress also correlate to obesity (Chaves Filho et al., 2018).

The current strategies for management of obesity and obesity-related disorders are classified in three main categories: lifestyle changes, pharmacological therapy and bariatric surgery (Haslam, 2016). Diet with caloric restrictions and increase in the daily physical activity are the first-line measures for obesity, but require period of months to get the first significant results. Addition of anti-obesity drugs to the lifestyle interventions increase the weight loss with about 3–5% compared to diet or exercises alone (Srivastava and Apovian, 2018). However, the pharmacotherapy of obesity is comprised from very short list of approved drugs associated with certain safety considerations and great variability between individuals in their response to the treatment (Manning et al., 2014; Srivastava and Apovian, 2018).

The natural multi therapy approaches have been accepted worldwide and during the recent decades a renewed interest in utilization of numerous plant extracts and individual phytochemicals or combinations of them as potent weight reducing agents with beneficial effect over obesity disorders has been observed. Evaluating plants from the traditional herbal medicinal systems supported with science-based evidences for their efficacy, safety profile, and mechanisms of activities is a required process to elucidate new potent bioactive leads (de Freitas Junior and de Almeida, 2017; Martel et al., 2017; Yun, 2010).

In the present review some of the advances in the pathophysiological mechanisms involved in obesity, as well as, novel therapeutic targets are discussed. Additionally, recent data on plant-based extracts and isolated compounds with anti-obesity potential are considered, explicating the most promising mechanisms to manage obesity from the perspective of in vitro, in vivo, and clinical studies.