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Published in final edited form as: Obesity (Silver Spring). 2009 Dec;17(0 3):S27–S33. doi: 10.1038/oby.2009.385

Exercise, Abdominal Obesity, Skeletal Muscle, and Metabolic Risk: Evidence for a Dose Response

Cris A Slentz 1, Joseph A Houmard 2, William E Kraus 1,3
PMCID: PMC3762482  NIHMSID: NIHMS501840  PMID: 19927142

Abstract

The obese are at increased risk for cardiovascular disease and type 2 diabetes. However, some who are obese have no metabolic abnormalities. So, it is not adipose tissue per se, but perhaps where it is located that is important for determining metabolic consequences. Regular exercise is known to reduce risk for metabolic disease through numerous mechanisms. The purpose of this report is to highlight some of the efficacy-based data on the effects of exercise (and also a sedentary lifestyle) on abdominal obesity, visceral fat, and metabolic risk. We also discuss how impaired fatty acid oxidation (FAO) in skeletal muscle may be related to both insulin resistance and a contributor to weight gain. In summary, it is evident that exercise in sufficient amounts can lead to substantial decreases in body weight, total body fat, and visceral fat. Additionally, evidence now supports the conclusion that there is a dose–response relationship between exercise amount and these changes, i.e., more exercise leads to additional benefits. Additionally, there are a number of important cardiometabolic risk factors that were most favorably effected by moderate-intensity compared to vigorous-intensity exercise. Unfortunately, it is also apparent that in sedentary middle-aged men and women, short periods of physical inactivity lead to significant weight gain, substantial increases in visceral fat, and further metabolic deterioration. Finally, favorable modulation of mitochondrial oxidative capacity in skeletal muscle by exercise training may reduce a block for complete oxidation of fatty acids in muscle and thereby relieve a block to effective insulin signaling.

In general, individuals who are obese are at increased risk for cardiovascular disease and type 2 diabetes. However, some individuals who are obese have no metabolic abnormalities, such as insulin resistance. It is clear that it is not fat or adipose tissue per se that is the issue, but perhaps where the fat is located that is important for determining dysmetabolic consequences. Research has firmly established that abdominal obesity (1) and especially increased levels of visceral fat (2–5) are more highly associated with metabolic disease risk.

Regular exercise is known to reduce risk for cardiovascular disease and type 2 diabetes through numerous mechanisms. It reliably and robustly improves insulin sensitivity and cardiovascular fitness (6,7), reduces blood pressure (8,9), improves dyslipidemia (10,11), and both individual and combined factors of metabolic syndrome score (12,13). Regular exercise has modest effects on reducing body weight with substantially greater effects on improving body composition. Conversely, it is becoming increasingly clear that a continued sedentary lifestyle in overweight or obese individuals—particularly those who already have some metabolic abnormalities—comes at a high metabolic cost, as numerous health-related variables worsen over relatively short time periods (12,14–16).

The purpose of this report is to highlight some of efficacy-based data on the effects of exercise (and also of continued inactivity) on abdominal obesity, visceral fat, and health-related metabolic risk variables. In addition to the important role of upper body obesity, we also briefly discuss how impaired fatty acid oxidation (FAO) in skeletal muscle may be related to both insulin resistance and a contributor to risk of weight gain.

The Short-Term Detrimental Effects of Physical Inactivity

A sedentary lifestyle over several years is associated with increased risk for type 2 diabetes, cardiovascular disease, and premature mortality (17–20). What is much less appreciated is the high cost of physical inactivity even in the short term. Booth et al. have been drawing attention for years to the societal and individual burden of inactivity-related chronic diseases (15,21,22). They remind us that while exercise is a treatment to prevent many chronic diseases, it is the lack of regular exercise or physical inactivity that is one of the actual causes of many of these diseases. Particularly relevant to this review, Booth’s group recently reported that cessation of exercise led to significant increases in intra-abdominal fat within just 21 days in an animal model (23).

In (Studies Targeting Risk Reduction Intervention through Defined Exercise—a randomized, controlled trial) we studied the effects of different amounts and intensities of exercise training for ~8 months on numerous cardiometabolic risk factors. It soon became obvious that there were numerous detrimental effects accruing in the inactive control group over only 6 months. We observed small but significant weight gain, sizeable increases in visceral fat. The weight and visceral fat gain was accompanied by additional metabolic deterioration within 6 months of continued inactivity. In Table 1, we show 12 health-related variables that were observed to worsen significantly (P < 0.05) in the inactive control group.

Table 1.

Effects of 6 months of continued physical inactivity in sedentary individuals

↑ Body weight ↑ Total abdominal fat ↑ LDL particle #
↑ Waist circumference ↑ Fasting insulin ↑ Small dense LDL
↑ Waist-to-hip ratio ↓ Insulin sensitivity ↓ LDL size
↑ Visceral fat amount ↓ Fitness (TTE) ↑ LDL-cholesterol
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Results above were taken from previously published results from STRRIDE (6,11,12,29,45).

Hamilton et al. have addressed the problem of inactivity from a somewhat different perspective. In an important paper (16), they present a compelling and well-developed case that society has not reached the pinnacle of non-exercise-related physical inactivity and inactivity-related morbidity and mortality. Specifically, they suggest that individuals, who are already nonexercisers and are not physically active, can reduce total activity even further. Their case is based on the well-grounded assumption that individuals who do not currently exercise can still become even more inactive due to expected continued technological advances that almost certainly will lead to increases in daily sitting time.

Exercise, Body Weight, and Composition—Evidence of a Dose–Response Relation

It is clear that decreases in physical activity play an important role, perhaps even a dominant role (24–26), in the rapid increases in obesity prevalence over the past few decades. However, the amount of activity needed to prevent weight gain is not known. Although previously controversial, it is now evident from numerous studies that moderate amounts of regular exercise can and does lead to moderate weight loss and even more significant fat mass loss when undertaken by previously sedentary individuals (27–29). Exercise studies have typically been conducted on lean individuals, or if they were with overweight/obese individuals; the exercise stimulus in terms of total weekly caloric expenditure was often quite small. This led to the mistaken perception that regular exercise will only result in modest weight loss. In a classic study of exercise-only vs. diet-only interventions, Ross et al. (18) compared an exercise stimulus (700 kcal expended per day, 7 days a week for 14 weeks) that was, for the first time, equivalent to the diet intervention (reduced caloric intake of 700 kcal per day for 14 weeks). This was important because the typical diet vs. exercise comparison generally involves a substantial caloric deficit through diet vs. a very modest exercise intervention and as a result, diet is generally considered the only way to lose weight. In this study in men, both interventions reduced body mass by 7.5 kg (~8%). In another study of similar design, this time in women (this time 500 kcal/day change in caloric balance with diet vs. exercise), Ross et al. (30) reported a weight loss of ~6.5%. These data show that weight loss is similar when the same degree of negative energy balance is produced by diet alone compared with exercise alone.

In a 2001 review, Ross and Janssen (31) presented data identifying a dose–response relationship between exercise amount and reductions in both fat mass and body weight loss. That is, when sedentary individuals begin a regular exercise program, they lose weight, and the more exercise they do, the greater the weight and fat mass loss. At the time of this 2001 review, no randomized, controlled studies had been conducted that actually directly tested the effects of two different amounts of exercise vs. a control group. Although STRRIDE was designed to investigate the effects of the different amounts and intensities of exercise on cardiovascular risk factors in middle-aged, overweight and mildly obese men and women with mild-to-moderate dyslipidemia (32), this design also allowed us to study the effects of these three different exercise interventions on several markers of body habitus. Briefly, out of 387 subjects recruited, 260 subjects completed the randomized, controlled trial of the effects of either a control group or one of three different exercise-training interventions: (i) low-amount/moderate-intensity group; the actual exercise prescription was to do 14 kcal/kg body weight/week of exercise at 50% peak VO2, equivalent to walking 12 miles/week; (ii) low-amount/vigorous-intensity group; the actual exercise prescription was 14 kcal/kg/week of exercise at 75% peak VO2, equivalent to jogging 12 miles/week; (iii) high-amount/vigorous-intensity group; the actual prescription was to do 23 kcal/kg/week at 75% peak VO2, which was equivalent to jogging 20 miles/week. This design allowed us to compare groups 1 and 2 to determine whether there was an exercise intensity effect and groups 2 and 3 to determine whether there was a dose–response effect, i.e., whether more exercise was better.

With regard to body weight, we found that even without changes in diet, 73% of our overweight or mildly obese subjects were able to prevent weight gain or experience modest weight loss with 180 min of moderate-intensity exercise each week (29). Moderate amounts of exercise also led to significant loss of total body fat mass (Figure 1). More activity (the high-amount group) resulted in greater weight loss, fat loss, and reductions in measures of central obesity (Figure 1). There was no significant effect of exercise intensity as the low-amount of vigorous exercise led to approximately the same weight loss and fat mass loss as an equal amount of moderate-intensity exercise (group 1 vs. 2). This study along with the studies by Ross et al., clearly showed that a calorie is a calorie—whether a moderate- or vigorous-intensity exercise calorie or whether a diet vs. exercise calorie. When taken together, these studies indicate that, with regard to exercise, weight change is all about the degree of caloric imbalance created through the exercise program (with moderate or vigorous intensity), and importantly, that exercise can be as effective as diet for weight loss.

Figure 1.

Figure 1

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Relationship between amount of exercise per week and (a) body weight change, (b) fat mass change, and (c) visceral fat change. Figure adapted from data from Slentz et al. (37).

Total and NonExercise Physical Activity Energy Expenditure

No discussion of the effects of exercise on body weight would be complete with discussing whether an exercise program leads to a compensatory reduction in other physical activity. Although it is widely assumed that incorporating an exercise program into one’s daily routine will increase overall physical activity, the literature on this issue is not conclusive. Meijer et al. (33) and Goran et al. (34) demonstrated that total daily energy expenditure in “elderly” subjects (average age 58 years and 66 years, respectively) was unchanged at the end of 12- and 8-week training programs, concluding that reductions in nonexercise physical activity compensate for exertion during exercise sessions. However, in a study by Meijer et al., younger subjects preparing for a half marathon demonstrated an increase in total physical activity energy expenditure (PAEE), but with no significant change in nonexercise physical activity, i.e., no compensation in other activity (35). This may suggest that although younger individuals may not compensate, perhaps middle-aged and older individuals do. However, we recently reported (36), from the STRRIDE study on subjects who were 40–65 years of age, that there was a clear increase in total PAEE/h with no evidence of compensation by reducing other physical activities—in fact there was a tendency for nonexercise physical activity to increase too (albeit not quite significant). This is certainly consistent with the observed decreases in body mass and fat mass in all three exercise groups, which could not occur if increased exercise expenditure was compensated for by reductions in other physical activity (37). We believe that the 8-month duration of our exercise-training program principally differentiates it from those that demonstrated no change in total PAEE. This longer training program is much more likely to replicate the chronic effects of regular exercise than a program of a few months or less. We hypothesize that the effect of an exercise program on total and nonexercise PAEE depend on the duration of that program.

Effects of Exercise on Visceral Fat

The unique importance of visceral fat and its consistent associations with risk factors for coronary heart disease and type 2 diabetes is well established. Visceral fat compared to total body fat is a significantly better correlate with triglycerides, systolic and diastolic blood pressure, high-density lipoprotein (HDL)/total cholesterol ratio and area under the insulin curve in response to a glucose challenge. Visceral fat has been shown to explain approximately twice the amount of variance in these variables when compared to total body fat (38,39). Comparing lean insulin-sensitive subjects to lean insulin-resistant subjects and to obese insulin-resistant subjects, Despres et al. data show that differences in visceral fat explain much of the atherogenic lipoprotein profile that is associated with obesity and insulin resistance (40). However, whether visceral obesity is causally related to disease or simply associated is controversial (41,42). Either way, the consistent, significant associations between visceral adipose tissue (VAT) and risk factors for coronary heart disease and type 2 diabetes indicate that it is a good marker of increased risk for these diseases.

There are a number of excellent, well-designed studies that have studied the effects of exercise on VAT. In a 12-week study in overweight men, Ross et al. (18) reported that an exercise program designed to increase energy expenditure by 700 kcal/day for 12 weeks resulted in a weight loss of 7.5 kg and a decrease in VAT of 52 cm2 (reported as the cross-sectional area of fat on a single-slide computed tomography scan), corresponding to a decrease of 6.9 cm2 VAT fat per kilogram of weight loss. The men in their diet-only group (700 kcal deficit) had a smaller but similar decrease of 5.9 cm2 per kilogram of weight loss. In STRRIDE, the men in the high-amount exercise group experienced a reduction of 5.6 cm2/kg of weight loss (6). Irwin et al. (43) studied the effects of a 12-month exercise program in overweight postmenopausal women. In this study, they used a significant exercise exposure consisting of at least 45 min of moderate-intensity exercise, 5 days/week for 12 months. They reported a loss of 8.5 cm2 of VAT and 1.3 kg of body weight, corresponding to a ratio of 6.5 cm2/kg of weight change. In the high-amount exercise group from STRRIDE, the women lost 6.9 cm2 of VAT per kilogram of body weight (6).

Although it is clear that sufficient exercise can lead to reductions in VAT, at the time of the 2001 review, Ross and Janssen concluded that there were insufficient data to determine whether there is a dose–response relationship between exercise amount and changes in VAT. Data from STRRIDE revealed that the middle-aged men and women in the inactive control group appeared to fairly aggressively increase visceral fat during the control period, whereas both of the low-amount exercise groups prevented this increase (with no apparent effect of exercise intensity) and the high-amount group led to significant and sizeable decreases in VAT (Figure 1). These data confirm that there is a dose–response relation between amount of exercise and changes in visceral fat. A 2008 review found that there is now adequate data to conclude that there is a dose–response relationship between VAT change and exercise amount.

Does exercise lead to preferential reductions in visceral fat over abdominal subcutaneous fat and/or does exercise lead to a preferential reduction in central vs. peripheral fat? This is a controversial question as some studies have shown a preferential reduction in central vs. peripheral fat (27,44). However, we did not observe a preferential reduction of central fat in any of the three exercise groups (37). Instead, all three groups experienced similar percent reductions in both central and peripheral skinfolds. Neither did we observe a significant change in waist-to-hip ratio in any exercise group. Interestingly, we did see that in the inactive control group there was a preferential deposition of fat in the central vs. peripheral depot as indicated by a significant increase in the waist-to-hip ratio.

How Much Exercise is Enough for Health Benefits?

The answer depends on both the variable of interest and the population being studied. Exercise physiologists and health professionals have long suspected that the amount of exercise needed would very likely depend on the health-related variable in question. Our experience from STRRIDE would support this notion. In Figures 1 and 2, we present the STRRIDE data represented another way (i.e., here, the data are plotted by exercise amount instead of by group—see Figure 3 for example of data plotted by group) to represent the relationship between exercise amount and body habitus changes in Figure 1, and changes in lipoprotein variables (lipoprotein particle size and number) the data from the figures of HDL and LDL size above) in Figure 2. In each of the three graphs to the left, the curve crosses the x-axis at different places. The point where the graph crosses the x-axis suggests how much exercise is needed just to prevent the deterioration seen with continued sedentary living—i.e., the “break-even” point—and that above this point, improvements begin to accrue. For both visceral fat (Figure 1c) and LDL particle change (Figure 2a), the graphs would suggest that to decrease VAT or the LDL particle number would require approximately >13 miles of exercise per week. However, changes in fat mass (Figure 1b) and the size of the LDL particles (Figure 2b) were more responsive to exercise, with the data suggesting that amounts >4 miles (for fat mass) or 7 miles/week (for LDL size) would start to return benefits. The amount of exercise needed to lose weight (>8 miles/week) or increase HDL size (>10 miles/week) fell somewhere in the middle.

Figure 2.

Figure 2

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Relationship between amount of exercise per week and (a) low-density lipoprotein (LDL) particle number change, (b) LDL size change, and (c) high-density lipoprotein (HDL) size change. Data from Kraus et al. (11). Figure reprinted with permission from Slentz et al. (60).

Figure 3.

Figure 3

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Effect of exercise amount and intensity on metabolic syndrome score. Figure reprinted from Johnson et al. (12) with permission from Elsevier. NSD, no significant difference.

Where Moderate-Intensity May be Better than Vigorous-Intensity Exercise

Interestingly, three important diabetes risk–related variables were improved more by moderate-intensity than vigorous-intensity exercise. Moderate-intensity exercise was significantly more effective at lowering triglycerides (TGs) (12) and improving insulin sensitivity index (45) than was vigorous exercise (see Figure 3, in ref. 46). These patterns (moderate-intensity better than vigorous) were observed for both men and women (data not shown). Also, metabolic syndrome score improved significantly with low-amount/moderate, but did not with low-amount/vigorous-intensity exercise (12) (see Figure 3). Finally, in part of the STRRIDE study that was designed to separate the acute from the sustained effects of exercise, it was of interest that moderate-intensity but not vigorous-intensity exercise resulted in sustained TG lowering (12). Only the low-amount/moderate-intensity group experienced significantly lower TGs after 5 and 14 days of no exercise. Both vigorous exercise groups returned to baseline soon after exercise training stopped. Although the mechanism(s) are yet not clear, it seems likely that either lipoprotein lipase activity was increased more (resulting in increased TG clearance) or that overall liver very low–density lipoprotein production was reduced more by moderate-intensity exercise.

Is Exercise Amount or Exercise Intensity More Important?

Although the above findings suggest that moderate-intensity exercise may be more effective than vigorous-intensity exercise for some health-related variables, it is important to remember that even for these variables there was a dose–response relationship between amount of exercise and magnitude of the benefit (albeit for vigorous intensity only, as STRRIDE was not designed to study dose response for moderate-intensity exercise). The major and most consistent findings from STRRIDE was that a modest amount of exercise (vigorous or moderate intensity) was better than no-exercise and that the largest and most widespread benefits were observed in the group that did the most exercise. In layman’s terms, the most important message is that for health benefits in sedentary individuals, some exercise is better than none, and more is better than less. It is clear that the majority of research supports this concept as this is one of the major messages from the 2008 Physical Activity Guidelines for Americans from the United States Department of Health and Human Services (47).

Skeletal Muscle Fatty Acid Oxidative Capacity, Insulin Resistance, and Body Mass Homeostasis

Skeletal muscle is a metabolically active tissue that is critical to maintaining whole-body homeostasis and plays an important role in FAO. At rest, the oxidation of lipid contributes significantly to overall energy needs with most of the energy requirements of muscle being obtained via FAO, which is quantitatively important due to muscle mass. Factors that elicit a decrement in the ability to oxidize lipid in skeletal muscle would thus be anticipated to evoke profound changes in whole-body lipid and fat mass homeostasis.

There are limited prospective data indicating that a propensity for weight gain is associated with a low rate of lipid oxidation in skeletal muscle. In Pima Indians, Zurlo et al. (48) reported that a low capacity for fat oxidation, as measured with whole-body indirect calorimetry, was associated with an increased risk for weight gain. Similar findings were obtained by Marra et al. (49) who observed that weight gain in lean women was associated with a low rate of whole-body fat oxidation. Other work has supported the premise that a low rate of fat oxidation is predictive of weight gain in both lean and obese individuals (50).

Studies examining the effect of weight loss on substrate utilization in obese individuals have obtained similar results. Larson et al. (51) studied previously obese individuals who lost a mean of 57 kg via energy restriction and found that fat oxidation (as determined with indirect calorimetry) was significantly depressed in the weight-loss (postobese) group compared to weight-matched controls. Similarly, Kelley et al. (52) reported no change in the capacity for fat oxidation when determining substrate utilization across a skeletal muscle bed of obese individuals before and after weight loss. In postobese individuals, there is a decrement in fat oxidation during sub-maximal exercise as well as at rest (for review see ref. 53) and in extremely obese individuals, which persists after weight loss of ~100 kg (refs. 45,54–56). Measurements in skeletal muscle indicate a loss in lipid oxidative capacity in obese individuals, particularly extremely obese subjects (54,56).

Insulin resistance is a health concern in the obese. The coexistence of insulin resistance and a decrement in FAO in skeletal muscle sometimes coexist in obese individuals (for reviews see refs. 53,57). However, the mechanistic link between FAO and insulin resistance in the skeletal muscle of obese individuals does not yet exist. There is evidence suggesting that the accumulation of lipid within the skeletal muscle of obese individuals induces insulin resistance. Some work suggests that metabolites such as long-chain acyl CoA, diacylglycerol, and ceramide accumulate in the cytosol of the skeletal muscle of obese individuals. These intermediates then either directly or indirectly impair insulin signal transduction and/or the activity of enzymes involved in glucose utilization, which in turn induces insulin resistance (for review see ref. 58). The accumulation of these metabolically active lipid intermediates could be due, at least in part, to the disturbances in mitochondrial function the ability to completely oxidize fatty acids to acetyl-CoA. The accumulation of incompletely oxidized fatty acid metabolites, such as ceramide, interfere with insulin signaling and lead to insulin resistance (59).

In summary, it is evident that exercise in sufficient amounts can lead to substantial decreases in body weight, total body fat, and visceral fat. Additionally, evidence now supports the conclusion that there is a dose–response relationship between exercise amount and body weight, body fat, and visceral fat—i.e., that more exercise leads to additional benefits. There are a number of important cardiometabolic risk factors that were most favorably effected by moderate intensity compared to vigorous-intensity exercise. Additional research will be necessary to confirm these findings. Unfortunately, it is also apparent that in sedentary middle-aged men and women, relatively short periods of physical inactivity lead to significant weight gain, substantial increases in visceral fat, and further metabolic deterioration. Finally, exercise training–induced changes in mitochondrial oxidative capacity in skeletal muscle appear to improve insulin action by reducing the accumulation of incompletely oxidized fatty acids.

Acknowledgments

This work was supported by National Institute of Health grant HL-57354.

Footnotes

Disclosure

C.A.S. has declared no financial interests. J.A.H. has received grant support from Children’s Research Institute. W.E.K. has declared no financial interests.

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