Sarcopenic obesity: An appraisal of the current status of knowledge and management in elderly people

Abstract

Today's increased life expectancy highlights both age-related changes in body composition and a higher prevalence of obesity. Sarcopenic obesity (SO) is assuming a prominent role in cardio-metabolic risk because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). This review evaluates the related studies that have been published over the past 10 years in order to give an updated overview of this new syndrome. There is no consensus on the definition of SO due to the wide heterogeneity of diagnostic criteria and choice of body composition components needed to assess this phenotype. There is a growing body of evidence that the ethio-pathogenesis of SO is complex and multi-factorial, as the consequences are a combination of the outcomes of both sarcopenia and obesity, where the effects are maximised. In order to manage SO, it is important to make lifestyle changes that incorporate weight loss, physical exercise and protein supplementation.

Introduction

In developed countries, populations are becoming progressively older and life expectancy is steadily rising (1, 2). Consequently, there is an increased prevalence of reports of physical limitations (3). The aging process starts in the thirties and increases progressively in later life: we know that fat free mass (FFM) tends to decline with age, accompanied by a relative increase of total adipose tissue and muscle infiltration (4) even when body weight remains stable (5). Low physical capacity can predict long-term disability, institutionalization, and death (6).

The loss of skeletal muscle mass associated with aging was first given the term sarcopenia (from the Greek: sarx for flesh and penia for loss) in 1997 by Rosenberg (7). This loss of flesh is due to a reduction in motor unit number and atrophy of muscle fibers (8). Reduced muscle mass with aging is mainly attributed to smaller type II muscle fiber size (9), although there is no consensus on whether there is a selective loss of specific types of muscle fiber (10). Over the last decade, this definition has evolved, and a qualitative dimension has been added that focuses on decreases in muscle strength and function (11), suggesting a significant decline in the quality of muscle (12, 13).

Several new definitions have been suggested that associate sarcopenia with both loss of mass and strength. Cross-sectional and longitudinal studies have also been presented to promote different ways of diagnosing the condition (14., 15., 16.). In 2010, the EWGSOP developed a practical definition for age-related sarcopenia: “a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death” (15). Moreover, in the international literature it is widely reported that sarcopenia is associated with a spectrum of consequences including functional limitation, disability, falls and bone fractures, immunodeficiency (17–19), and impaired thermoregulation. Nowadays, the prevalence of sarcopenia varies from 5 to 13% in 60- to 70-year olds and 11 to 50% in the over 80s, and depends on what diagnostic methods and definitions are used (20, 21). This syndrome is theorized to be a multifactorial process promoted by disuse, altered endocrine function, protein and hormonal kinetics, chronic diseases, inflammation, insulin resistance, oxidative stress, and malnutrition (10, 22, 23).

Unsurprisingly, the age-related shifts in body composition (Figure 1) that affect sarcopenia also promote the development of obesity. Aging is associated with an increase in adiposity and a redistribution of body fat, often to ectopic depots. The redistribution of fat from lower-body subcutaneous depots to the abdominal or visceral region is often reported in the elderly and can occur independently of changes in total adiposity, body weight or waist circumference. Both of these muscle fat depots increase with age, and may be associated with deleterious health outcomes (24). Furthermore, both aging and obesity are associated with a progressive deterioration of muscle quality (25), and obesity is an important risk factor for frailty either through increased levels of inflammatory markers or through sarcopenia (26). The result is an insidious vicious cycle in which people become more obese and yet weaker, do even less physical activity (27), develop insulin resistance, with each part of the cycle reinforcing the next (28).

Figure 1.

Age-related shifts in body composition: as people age they lose the lean muscle mass gained in young adulthood (A), resulting in a higher proportion of fat mass (B), even if the absolute amounts of body fat remain constant (29)

Definition of sarcopenic obesity

Most of the literature focuses on the combination of obesity and low muscle mass, appropriately defined sarcopenic obesity (SO). Baumgartner et al. (30) proposed criteria for this new combined condition, according to which, individuals with SO have (a) an appendicular skeletal muscle mass index [ASMI: legs and arms muscular mass/height (m²)] <2 standard deviations in comparison to a young adult reference group aged between 20 and 30 years old and (b) a percentage of body fat above the 60th percentile for the same gender and age. However, a consensus on the definition of this body composition phenotype has yet to be reached, and the true prevalence of SO is unclear, partly because of variation in definitions and thresholds for determining low muscle mass and high fat mass (FM). Several other definitions were given by different authors, which diverge in terms of the parameter chosen as an indicator of FFM (i.e. appendicular skeletal muscle mass, muscle mass, fat free mass) and FM (i.e. body mass index, waist circumference, fat mass %), and also in terms of the diagnostic approach used to identify subjects with both sarcopenia and obesity. Definitions based on strength are more recent and present intrinsic challenges. The usual normalization of strength by body size or by fat mass conceals part of the discrepancy between the “engine” and the “mass to be moved”. Thus, operational definitions based on crude rather than “normalized” strength have been proposed. Although there are no generally accepted criteria for low muscle strength, measuring strength is easier and cheaper than measuring muscle mass. The use of more sophisticated methods such as DXA or computed tomography are kept as an option in more thorough clinical examination and especially in establishing the effectiveness of interventions (31). Table 1 shows the characteristics of the most relevant study definitions of sarcopenia, obesity and SO.

Table 1.

Characteristics of the parent study definition of sarcopenia, obesity, and sarcopenic obesity

AUTHORS	CHARACTERISTICS OF THE STUDIES
	Body composition and analysis method	Muscle mass definition	Sarcopenia definition	Obesity definition
BAUMGARTNER (32)	DXA	ASM/m2	ASM 2 SDs below sex-specific means of Rosetta study reference data (33)	% body fat
DAVISON (34)	BIA	Total body skeletal mass/ m2	Lowest two quintiles for relative muscle mass in included sample	% body fat
ZOICO (35)	DXA	Total body skeletal mass/ m2 (36, 37)	Lowest two quintiles for relative muscle mass in recruited cohort	% body fat
SCHRAGER (38)	N.A.	N.A.	Grip strength = lowest sex-specific tertile	Waist circumference: upper tertile BMI ≥ 30 kg/m2
BOUCHARD (39)	DXA	ASM/m2	ASM 2 SDs below mean for cohort of 60 young adults (30 male, 30 female) aged 20-35 years	% body fat
KIM (40)	DXA	ASM/m2 Total skeletal muscle mass x 100/weight ASM/m2	<2 SDs below sex-specific normal means for a young reference population <2 SDs below sex-specific normal means for a young reference population Lowest 2 quintiles of ASM/height2 in study population	% body fat
LEVINE (41)	DXA	ASM x 100/body mass	ASM x 100/body mass <2 SDs below 20- to 40-year-olds from NHANES 1999-2004	Waist circumference

Abbreviations: DXA = Dual-energy X-ray absorptiometry; BIA = Bioelectrical impedance analysis; ASM = appendicular skeletal muscle mass; SD = standard deviation; NAHNES = National Health and Nutrition Examination Survey (NHANES)

Differences associated with race and ethnicity in study populations may also alter the identification of sarcopenia and obesity, which may contribute to this variation (42, 43). In many cases, substantial increases in body fat and decreases in muscle mass are not clinically evident if a person maintains a relatively stable body weight. Indeed, data from the New Mexico Aging Process Study and the New Mexico Elder Health Survey demonstrate that sarcopenia, with its loss of muscle mass, occurs even when absolute amounts of body fat remain constant over time (29).

Fat accumulation and fat redistribution associated with muscle loss do not necessarily lead to an increase in body mass index (BMI). As a result, obesity is not diagnosed until the fat mass increases to such an extent that total body mass also increases. Therefore, Han et al. (44) suggest that waist circumference gives a better indication of adiposity and SO than BMI. Furthermore, there is usually some height loss with aging, making BMI data even more difficult to interpret in the elderly.

Etiology

There is a growing body of evidence that the ethiopathogenesis of SO is complex, as many factors can interplay, including lifestyle (diet, physical activity, smoking), hormones (growth factors, insulin, vitamin D), oxidative stress, neuromuscular changes, vascular (endothelial function, coagulation) and immunological (proinflammatory cytokines) factors, and other factors that have yet to be identified (42, 45). Due to multiple age-related physiological mechanisms, body composition changes. These alterations seem to be strongly connected to each other from a pathogenetic point of view, and aging is also associated with a decline in a variety of neural, hormonal and environmental trophic signals to muscle (46).

Between the ages of 20 and 70, FFM decreases progressively, then after the age of 70, FFM and FM decrease in parallel. In addition, fat distribution alters with age: visceral fat and waist circumference increase, whereas subcutaneous fat decreases. Fat is also increasingly deposited in skeletal muscle and in the liver (47, 48). Sarcopenia is a silent progressive phenomenon as muscle loss can sometimes be masked by weight stability. Nevertheless, a remarkably consistent characteristic of aging, even in those who lose weight, is the gain in muscle fat infiltration (4).

The higher visceral fat is the main determinant of impaired glucose tolerance in the elderly. Several studies demonstrated that visceral fat is an important site of secretion of the inflammatory mediators c reactive protein, interleukin-6, soluble interleukin-6 receptor, and interleukin-1 receptor antagonist (38, 39). Furthermore, these studies suggest that the distribution of fat mass is also important and that abdominal obesity is more proinflammatory than generic obesity, as it provides systemic inflammation. Therefore, increased intramuscular and intrahepatic fat contribute to impaired insulin action through locally released adipokines and fatfree fatty acids. In turn, adipokines secreted from fat tissue could promote muscle wasting and fatty infiltration (50). Elevated pancreatic fat with declining cell function also plays a role (47). During aging, elevation of inflammatory markers could be involved in the development of insulin resistance (51). Since insulin has impaired anabolic and antiproteolytic effects on muscle protein metabolism, a reduction of insulin sensitivity may affect protein degradation, protein synthesis, and ultimately muscle growth. Obesity may lead to sarcopenia by inducing anabolic resistance to amino acids, growth factors, and contractile activity, ultimately affecting protein turnover and growth of skeletal muscle (52). The fatty infiltration of muscle that occurs in obesity may cause an inflammatory environment within the muscle. In a highly inflammatory state, obese people preferentially mobilize muscle, not fat, and this represents a major contributor to fat gain, which in turn reinforces muscle loss. A cross-sectional study demonstrated that both insulin resistance and inflammation were significant factors for predicting SO in women (53). Finally, Kohara et al. (54) suggested that leptin may link visceral obesity and sarcopenia, because their study indicated that plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone.

It is well known that diet and nutritional status also have a real influence on body composition and physiological pathways. For example, evidence shows that in the American population there is a trend for decreased protein intake, although the percentage of calories from protein increases slightly in older Americans (55). Even healthy older adults appear to exhibit a significant loss of the ability to regulate food intake. When combined with a reduction in chemosensory perception and disadvantageous social factors, the anorexia of aging may contribute to many negative consequences in this population, such as the loss of skeletal muscle mass, micronutrient deficiencies, frailty and accelerated mortality (56).

Consequences

Sarcopenia and obesity often coexist in elderly individuals. Loss of muscle fibers due to sarcopenia leads to deterioration of muscle mass, and reduced physical activity and energy expenditure. Alterations in the expression of myogenic regulatory factors may impair the ability of aged muscle to repair damage. Low muscle mass is associated with decreased survival rates following acute illness and with a doubled risk of nosocomial infection in the care of the elderly (18, 57). Sarcopenia is known to be associated with adverse glucose metabolism and metabolic syndrome, which are important risk factors of cardiovascular disease (CVD) (58, 59).

On the other hand, obesity alone and its related consequences is perhaps one of the most comprehensively studied and debated modern epidemics. Inter alia, abdominal and visceral obesity are related to an increased risk of type 2 diabetes, hypertension, dyslipidemia and CVD (60–62). Despite these adverse outcomes, some studies showed that in old population obesity may protect against mortality. Janssen et al. (62) demonstrated that higher BMI values indicate a lower mortality risk, but if obesity is combined with low muscle strength, the risk of mortality may exceed the protective effect.

In SO, sarcopenia and obesity might synergistically increase their effects on physical disability, metabolic disorders and CVD. In addition to each component's individual implications, the adverse health effects of sarcopenia and obesity may be additive, leading to both more functional limitation and metabolic disorders. For example, SO was associated with a 23% increased risk of CVD in a large sample of communitydwelling elderly adults (61). The loss of flesh and excess of adiposity determine physical impairment, reduced physical performance (63) and overall quality of life, chemotherapy toxicity and shorter survival in cancer patients (64), and chronic inflammation (38, 53, 65) in comparison to individuals with normal body composition. In addition, Honda et al. showed that SO was associated with inflammation and increased mortality in patients with end-stage renal disease (66).

In general, sarcopenia and abdominal obesity are associated with all-cause mortality, with the highest risk in sarcopenic obese men (67). In 2015, the cross sectional study by Kim (60), in accordance with most of the studies conducted on the health implications of SO (61), found that both men and women with SO had a higher risk of CVD than those with a normal BMI and muscle mass. Furthermore, the vicious cycle between the loss of muscle and the accumulation of ectopic fat might be associated with atherosclerosis via a complex interplay of factors, including proinflammatory cytokines, increasing insulin resistance, dietary energy, physical activity, oxidative stress, mitochondrial dysfunction, and other factors that have yet to be identified (68).

Although SO is an issue of great relevance, the impact of this condition on health has been poorly studied and the literature is conflicting. The discrepant findings may be due to the different approaches for assessing SO and population characteristics, such as ethnic differences (60). The most debated question is whether muscle mass or strength is more important for cardiovascular health. A prospective study shows that the conflicting results between different definitions of SO imply that muscle quality is more important than muscle quantity in aging humans (69). The lack of a unified definition for SO might contribute to inconsistent findings about the association with the related adverse outcomes and SO may be more frequent, but underestimated among older individuals.

Management

The phenotype for sarcopenic obesity is decreased muscle mass and strength, and increased fat depots, particularly abdominal fat. Given the clinical presentation, it is not surprising that obesity management has traditionally focused on decreasing weight rather than increasing muscle.

The treatment should focus on three different aspects that jointly contribute to better health: weight management, physical activity and nutritional supplementation. Weight management mainly aims to reduce intra-abdominal fat through diet restriction; on the other hand, muscle mass and strength can be preserved by physical activity and protein supplementation. It is well known that the causes of SO are interrelated, so interventions are not limited to a single cause.

Weight loss

There is increasing prevalence of chronic illnesses with aging, many of which are associated with nutritional changes. Intentional weight loss in obese patients can improve or prevent many of the obesity-related risk factors for CVD (70). Current therapies available for weight management that cause weight loss by inducing a negative energy balance include dietary intervention, physical activity, pharmacotherapy, and surgery. Behaviour modification to enhance dietary and activity compliance is an important component of all of these treatments (70). Additionally, weight reduction in the elderly can have clinically important benefits with regard to osteoarthritis, physical function and type 2 diabetes mellitus (71). On the contrary, excess caloric intake that results in obesity might accelerate sarcopenia by causing high levels of oxidative stress. The immoderate intake of high-calorie, rapidly digestible food leads to abnormal surges in serum free fatty acids and glucose levels, which are linked to the increased generation of reactive oxygen species (68). Mazzali et al., 2014 (72) observed that a moderate weight loss determines a significant improvement in insulin resistance, fat distribution and, more importantly, in muscle lipid infiltration. Furthermore, correct weight management helps to maintain or improve physical capacity in older men and women (6). The position statement on obesity in older adults by the American Society of Nutrition (ASN) and the Obesity Society provides two ranges of daily energy deficits for a weight loss regimen. A 500–1,000 kcal/day reduction is given as a treatment guideline to achieve a weight loss of approximately 0.4–0.9 kg (1–2 lb)/week, while a modest reduction in energy intake of 500–750 kcal/day is provided as a recommendation (73).

In summary, energy restriction alone appears to successfully produce a moderate loss in body weight, but this success can be costly in terms of losses in FFM. The addition of exercise to energy restriction does not appear to have an additive effect on the amount of weight lost, but it can attenuate the loss of FFM (74) since energy restriction alone appears to successfully produce a moderate loss in body weight, but this success can be costly in terms of loss of FFM. Tiffany et al., 2008 (75) showed that the addition of exercise training to diet reduces the amount of muscle mass loss during voluntary weight loss in frail obese older adults and significantly increases muscle strength. Moreover, a weight management strategy also seeks to retain as much lean body mass as possible through increased protein intake and resistance exercise (71). Diet can be combined to physical exercise to further improve the health status of an individual with sarcopenic obesity. Effective long-term weight loss depends on permanent changes in dietary quality, energy intake and activity (76). A 1-year, randomized, controlled trial suggests that a behavioural therapy for weight loss combined with exercise training provides greater improvement in function and frailty in obese older subjects than either intervention alone (77).

Physical exercise

Sarcopenic obese elderly people have lower physical functional levels than healthy counterparts. Older individuals with low muscle mass have an increased risk of functional decline because their muscles are generally weaker. Reduction in muscle mass is an important determinant of physical function and metabolic rate and leads to the clinical hazards of obesity appearing at a lower BMI in older people. On the other hand, low muscle strength is associated with a higher risk of mobility limitations (3, 44). Pedrero-Chamizo et al., 2015 (78), demonstrated that higher levels of physical fitness are associated with a reduced risk of suffering SO and better perceived health among elderly. A longitudinal study showed that muscle mass can be effectively increased through prolonged resistance type exercise training, which can be entirely attributed to specific type II muscle fiber hypertrophy (9). Fast-velocity resistance exercise appears to be a novel intervention for older adults to enhance muscle power, which is a significant predictor of performing activities of daily living and is reduced with age at both slow and fast velocities (23). Interestingly, it has recently been shown that even in old age, endurance physical exercise may counteract muscle loss via the attenuation of skeletal muscle apoptosis (79). Resistance training diminishes the pathological progression of SO by offering a wide range of physiological benefits to skeletal muscle, including reduced inflammatory cytokines and increased mitochondrial function, while aerobic exercise also conserves muscle mass by improving muscle blood flow and decreasing oxidative stress (68, 80). Negro et al., 2011 (81) reported that strength training specifically recruits type II muscle fibers, producing anabolic responses of adaptation that are unachievable through aerobic workouts. Additionally, the Cardiovascular Health Study (CHS, 2009) showed that the increased risk of CVD associated with SO decreased from 23 to 18% after controlling for physical activity (61).

Thus, physical activity might be a good therapeutic intervention to interrupt the link between SO and cardiometabolic diseases. Weinheimer et al. (74) suggest that exercise is an effective tool to combat SO by helping obese men and postmenopausal women aged 50 years and over to preserve fat free mass after moderate energy restriction-induced weight loss. However, several authors disagree with the fact that diet can always maximize positive outcomes of physical exercise. For example, Lambert et al., 2010 (82) demonstrated that exercise decreases inflammatory cytokines toll-like receptor-4, interleukin-6 and tumor necrosis factor-alpha, while weight loss has no effect. Thus, exercise but not weight loss had a beneficial effect on markers of muscle inflammation and anabolism in frail obese elderly individuals.

In summary, resistance exercise has a high potential for the effective treatment of sarcopenia because it improves muscle performance and functional capacity as clinically important outcome parameters (22). Resistance exercise may help to eliminate the age-related deficits in muscle mass and strength and seems to be the most effective intervention to reverse sarcopenia in the elderly as it has been shown to be effective and safe even in very old and frail subjects (25). In a one-year, randomized, controlled trial involving obese older adults, conducted in 2011, weight loss plus exercise improved physical function and frailty (77). Furthermore, it was suggested that protein supplementation in combination with resistance exercise enhances muscle protein synthesis and improves body composition by increasing FFM in relation to FM (60). Interventions that utilize resistance training exercise in conjunction with increased protein intake appear to be promising in their ability to counteract osteosarcopenic obesity (83). Some ongoing trials are testing the effect of addition of whole body electromyostimulation or physical exercise and nutritional supplementation in people aged 65 and over (84, 85). However, little is known regarding the capacity of resistance training to counter the loss of muscle that accompanies voluntary weight loss in older adults (>65 years old) who are at risk of worsening sarcopenia.

Protein supplemention

A decrease in food intake by older adults can have overlapping causes and far-reaching effects. Dietary data suggest that many elderly people have a reduced appetite and fail to eat sufficient protein (55, 86) while they suffer from chronic diseases that further increase their protein needs (i.e. diabetes, low-grade inflammation). Other aspects that hinder the consumption of a healthy diet are social factors, economic hardships and functional difficulties, as well as physiological alterations to the taste buds and changes in digestion and absorption (87). In 2014, Oh et al. performed a cross-sectional study on the Korean population which demonstrated that despite being fairly healthy, the traditional dietary pattern has a low consumption of protein, calcium and vitamin D (88). Another problem is that the current recommendations for protein requirements were determined on the basis of studies performed on healthy individuals, so they may not be adequate for individuals with obesity in later life or as part of complex conditions such as SO. Additionally, hypocaloric diets for SO in older people should supply adequate protein, which may help to prevent muscle loss (89) and improve adherence to low energy intake (90). It has been established that increased protein intake will maintain muscle mass during calorie-restricted diets to a greater extent than usual protein intakes (91). Table 2 shows the different protein supplements available for sarcopenic obesity treatment. Protein intake may also be a significant factor for preventing the development of sarcopenia, in fact it was reported that nutritional supplements of oral amino acid mixtures increased the whole-body lean mass and insulin sensitivity in older adults with sarcopenia (60). The study of Levine et al., 2014 (92), highlights that at older ages, it may be important to avoid low protein intake and gradually adopt a moderate to high protein to allow the maintenance of a healthy weight and protection from frailty. In fact, it has to be taken into account that protein supplementation is useful for treating elderly sarcopenic obese patients. Nevertheless an excessive intake of protein could be very harmful for the 65 and younger population. It has been reported that people aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. Furthermore, high levels of IGF-1 increase even further these risks (92). The gastrointestinal peptide ghrelin beside increase appetite and food intake, stimulates growth hormone-insulin-like growth factor (GH/IGF-1) axis. A cross-sectional study examined the possible relationship between ghrelin and sarcopenia. However, the study did not allow a definitive conclusion (93).

Table 2.

Summary of protein supplementation

Supplementation
• Whey protein
• Branched-chain amino acids
• Leucine
•Hydroxy-beta-methylbutyrate
• Arginine
• Cysteine

The current mean dietary protein requirement for healthy male and female adults of all ages is estimated to be 0.6 g protein/kg/day, with a suggested safe level of intake set at 0.8 g protein/kg/day (94, 95). The question as to whether dietary protein needs to change with age is subject to scientific debate (96). Some experts suggest that a protein intake of 1.0 to 1.6 g/kg/day is safe and adequate to meet the needs of healthy older adults, reducing the risk of chronic diseases, and improving outcomes (86, 97). Other strategies include the use of highprotein meal replacements or specific ergogenic or branchedchain amino acid supplements (BCAAs) to reach specific goals such as the intake of 6g of EEAs per meal (98). Ensuring adequate dietary protein intake using high quality proteins is essential in adults with sarcopenic obesity, with the quality of the protein being more important than the quantity.

Whey protein (WP) is the collective term for the soluble protein fractions extracted from diary milk (99). It has been demonstrated that WP, and in particular the BCAAs it contains, are able to stimulate whole-body and muscle protein synthesis (71, 100). Thus, it could represent an effective countermeasure to prevent muscle atrophy associated with physical inactivity and muscle unloading during aging. Nevertheless, Katsanosa et al., 2008 (98) suggest that whey protein ingestion has a greater anabolic effect in the elderly than its EAAs. In the study by Coker et al., 2012 (101), whey protein (WP) and essential amino acids (EAAs) promoted a 30% greater loss of adipose tissue in sedentary older obese subjects during intentional weight loss. The ingestion of WP is expected to increase the plasma concentration of the amino acid cysteine, which has been described to have a particular role in enhancing muscle protein anabolism (99). In addition, the hepatic catabolism of this amino acid is a key regulator of whole body protein metabolism. L-cysteine supplementation has the potential to lower blood levels of glycemia and the markers of vascular inflammation c reactive protein and monocyte chemoattractant protein-1 (102).

The BCAA leucine has been reported to be a stimulating factor for muscle protein synthesis (103). One study demonstrates that attenuated response of muscle protein synthesis following ingestion of small amounts of amino acids can be reversed by the ingestion of extra leucine. Specifically, these data emphasize the important role leucine has in reversing the lack of response following the whey protein-based EAA mixture (104). Leucine appears also to regulate oxidative use of glucose by skeletal muscle through stimulation of glucose recycling via the glucose-alanine cycle (105). Betahydroxy- beta-methylbutyrate (HMB) is a metabolite of leucine that can improve this muscle loss. Several studies show that supplementing the diet with HMB is likely to improve the decrease in muscle protein synthesis and attenuate loss of muscle in older adults confined to bed rest. Another interesting potential mechanism of HMB to preserve muscle mass could be via the downregulation of muscle protein degradation. As well as performing an anabolic action, EEAs are known to have a positive effect on the entire metabolism. Lucotti et al., 2006 (106) showed that chronic L-arginine administration improved insulin sensitivity, endothelial function, oxidative stress and adipokine release in lean type 2 diabetic patients.

Conclusions

SO is a growing public healthcare problem because of the rapid expansion of the elderly population, the obesity epidemic, and a lack of a solution to this problem. Moreover, SO is more complicated than either sarcopenia or obesity alone, because it is not just the simple combination of sarcopenia and obesity (68). It may be clinically relevant to identify older adults with sarcopenic obesity, although its definition and clinical consequences require further studies. To this end, it is necessary to establish a unified definition of SO and standardized primary outcomes for SO. The molecular pathology of SO is difficult to unravel for several reasons and the etiopathogenesis is complex and multi-factorial. SO might be associated with cardiometabolic diseases and mortality, although these findings should be confirmed in future studies. This review suggests that the prevention and treatment of SO should be based primarily on lifestyle interventions. While there is convincing evidence that weight loss and exercise independently result in the reversal of sarcopenic obesity and frailty, an intervention strategy incorporating combined weight loss and exercise has proven to be the most effective treatment for this disorder. Furthermore, we suggest that an adequate high-quality protein intake in older adults could improve the effects of this syndrome. It is especially important to supplement a diet with WP in order to help to maintain muscle mass, and decrease insulin resistance, inflammation and oxidative stress. In conclusion, to prevent and treat SO, it is worthwhile to find the right energy balance between diet and exercise, in order to minimize the combined effect of obesity and sarcopenia.

Financial disclosure

None of the authors had any financial interest or support for this paper.

Conflict of interest

The Authors declare no conflict of interest.