Clinical Obesity in Adults and Children. Группа авторов

and associated disease [105], and the same is true of the circumpolar Inuit [106]. Likewise, individuals who, as infants, were fed milk formulas with protein content higher than human breast milk have increased susceptibility to obesity later in life [70]. Since formula‐fed infants cannot regulate the ingested balance of their diet, it is likely that they compensate post‐ingestively by reducing amino acid retention through upregulating gluconeogenic pathways. If elevated gluconeogenesis is retained into later life – i.e. is developmentally programmed – this would have the effect of increasing the protein target to compensate for reduced protein efficiency hence predisposing to obesity. Finally, muscle protein catabolism and hepatic gluconeogenesis are inhibited by insulin, and this inhibition is impaired in insulin resistance and when there are high levels of circulating free fatty acids. Obesity might thus itself predispose to excess energy intake via increased breakdown of muscle protein and hepatic gluconeogenesis, driving an increased protein intake target [53].

      Perhaps most important of all, as discussed next, protein leverage could provide a biologically grounded framework for focussing research aimed at unraveling the complex interactions between humans and food environments.

      Why do humans select low‐protein foods that cause energy over‐consumption?

      The protein leverage hypothesis simplifies the challenge of understanding how humans interact with food environments by explicitly distinguishing the two primary components of feeding regulation, which foods are selected and how much of each is eaten. Protein leverage addresses the second of these questions through attributing the over‐consumption of energy on low protein diets, such as those rich in ultra‐processed foods, to the strong human appetite for protein. In so doing, it highlights the importance for public health research of addressing the questions of why humans choose to eat low‐protein ultra‐processed foods that dilute protein resulting in excess energy consumption and how this can be managed. These questions, we believe, are the highest priority, both for understanding better how people interact with transitioning food environments to shape their diets and for formulating policy and other interventions to influence these interactions.

      There are many contributing factors. Important among these is that the industrial synthesis of edible products from highly refined ingredients, as in ultra‐processed foods, offers opportunities for customizing compositions in ways specifically designed to encourage consumption. One method is combining ingredients in ratios that are hyperpalatable, to dial in a “bliss point” that maximizes hedonic responses. This can be done, for example, by including carbohydrates and fats in ratios that are highly palatable, and intensifying the effect by increasing the concentration of the mixture through minimizing other components such as protein and fiber. Palatability can be further enhanced by adding salt or other flavor‐enhancers.

      Some of these manipulations not only target the food choice component of diet regulation, but also influence or interact with the amounts eaten. For example, high palatability can itself stimulate appetite and delay satiety [107]. Increasing the ratio of fats and carbohydrates to protein to increase palatability will also result in increased consumption via protein leverage, an effect that will be exacerbated when the other major satiating dietary component, fiber, is also low [62]. Using a formula that integrates the protein, fiber, fat, and energy density of foods to calculate satiety potential, Fardet et al. [108] showed that ultra‐processed foods are significantly less satiating than other foods.

      A particularly insidious processing strategy is to impart a savory flavor on low‐protein foods. In humans, like other species, an important mechanism for nutrient balancing is to selectively seek foods rich in nutrients that are currently deficient in the diet. Savory‐flavored snacks, like meat‐flavored potato crisps or cheese‐flavored crackers, act as “protein decoys,” which are attractive when protein deficient, but rather than rebalance the deficiency, they exacerbate it through their high fat and carbohydrate content [109]. The resulting protein dilution can further drive energy over‐consumption through protein leverage. An illustration of this is the finding discussed above that subjects restricted to low‐protein diets in the experiments of Gosby et al. [57] over‐ate energy principally via snacking on savory foods between meals.

      In addition to the formulations themselves, many other factors encourage the consumption of ultra‐processed foods. These include their convenience and relatively low price, the latter partly due to the low content of protein which is more expensive than fats and carbohydrates [110]. Aggressive marketing is an important factor at all scales from local food advertising and promotion to sophisticated global strategies facilitated by the transnationalization of advertising agencies and exploitation of new media technologies [111]. Marketing strategies include the “health halo” effect, in which misleading claims or imagery manipulate consumers into associating products with healthfulness. Marketing budgets of multinational processed food and beverage companies are immense. In 2018, the Swiss food and beverage producer Nestlé is reported to have spent US$7.3 billion on global advertising, and US$1.9 billion more than that in 2016 [112].

There is growing evidence that corporate political activity, whereby industries influence government policy, research, and dietary guidelines for their own benefit, significantly impedes the formulation and implementation of public health policies for reducing the intake of problem foods [103,113–115]. A recent analysis documented the strategies used by one company, Nestlé, to market processed breastmilk substitutes [116]. Strategies included: “‘information strategy’, used to fund, produce and disseminate industry‐preferred information” “[establishing] relationships with key opinion leaders and health organizations, and the media” “[seeking] involvement in the community” “directly [influencing] policies and programs through indirect access and the placement of actors in government policy settings” and using “argument‐based ‘discursive strategies’ to frame the debate on a diet‐ and public health‐related issues.”

      Having reported in 2018 an annual turnover of over 92.6 billion CHF (US$101 billion) and an underlying trading operating profit of 16.3 billion CHF (US$17.9 billion), Nestlé is well resourced to execute such strategies. This is not, however, an isolated case. Similar tactics are widespread in the food industry, as in other industries where there are potential trade‐offs between public interest and corporate profit [114,117]. Collectively, their capacity to influence the global food systems and food environments is immense.

Bringing it all together: complex systems

      Linking public health to the science of ecology is important, because it provides a bridge for the transfer of concepts and methods that could potentially enrich both fields. Nutritional geometry is one example, demonstrating how approaches from animal studies, both in the laboratory and in the wild, could provide fresh insight into major public health challenges, such as the obesity epidemic. Another example is the link between the “ecosystem” concept from ecology and the “food systems” concept in public health, mentioned above. We believe that the combination of these approaches holds considerable promise for reconceptualizing and potentially reversing the obesity epidemic.

      As noted previously, one defining feature of the concept of the ecosystem is that it provided a framework for elevating ecological thinking beyond organisms to the broader system that includes both biological and non‐biological aspects of the environment [78]. This integrative approach inevitably directed the attention of ecologists towards questions of how the interactions among the component parts of the system influence the properties and behavior of the system, a quest that has yielded many powerful ecological insights that are relevant also to public health.

      One key insight is that the properties of interacting components of ecosystems (e.g. individuals, populations, species) can be changed as a result of their interactions with other components through a process known as “adaptation”. Those changes can reverberate through the system, eliciting adaptations in other interacting components, which can drive further changes in the first, producing a dynamic reciprocal process known as “coevolution” [118]. Important properties of ecosystems, such as the degree of stability and productivity, “emerge” from these adaptive and coevolutionary dynamics among its components. The ecosystem‐level