Abstract The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake (“eat less”) and increase energy expenditure (“move more”). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on “complex endocrine, metabolic, and nervous system signals” that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, “ultra-processed” foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body’s metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.
Eating requires at least two basic decisions: what to eat, which is a decision about food choice, and how much to eat, which is a decision about food intake. This distinction is important because food choice and intake involve different behaviors, different controlling signals and different physiological mechanisms. Feeding behavior is controlled by a variety of signals. ‘Cephalic’ signals, such as the taste, smell, sound and sight of food, control food choice and can influence the amount of food consumed in the shortterm. Gastrointestinal signals resulting from changes in distention or the release of gut peptides may play a role in the control of shortterm intake within a meal or across several meals. Metabolic signals generated by the supply and utilization of metabolic fuels not only influence food choice, but also how much food is consumed in the short-term. Metabolic signals also determine food intake in the longterm and are important in maintaining energy balance over a nutritionally significant interval. Traditionally, research emphasized separate signals associated with glucose and fat metabolism. ‘Glucostatic’ hypotheses about these signals have focused on either changes in the circulating level of glucose or on intracellular glucose utilization, whereas ‘lipostatic’ hypotheses have targeted the amount of body fat or, more recently, the adipose hormone, leptin. A less well known line of research has looked to metabolic processes common to the metabolism of both glucose and fat for metabolic signals controlling food intake. This perspective was initially proposed by Ugolev and Kassil (1961), who investigated the tricarboxylic acid cycle as a source of a common, ‘oxidative’ metabolic signal. More recently, research in this area has focused on aspects of ATP production. Our approach to the study of the metabolic controls of food intake addresses questions that are usually associated with the study of sensory systems: Where are receptors/detectors that monitor metabolic events to control food intake? What stimulus is adequate to activate the receptor? How is this stimulus transduced into a neural signal? And how is this signal transmitted to and within the central nervous system? Here, we review our laboratory’s work on each of these issues in turn.
Page 192: Michael E. Tordoff and Mark I. Friedman. “Hepatic portal glucose infusions decrease food intake and increase food preference.” Page R195: first paragraph, the first four sentences should read In addition to the theoretical implications of these results, several practical implications are apparent. The data suggest that repeated tests of the same subject must be interpreted with caution, because the response during later tests may well be determined by previous infusions. It is interesting to note in this regard that several previous studies finding no change in feeding after hepatic portal glucose infusion have used daily tests according to counterbalanced designs (Refs. 2, 13, and 17–20 and perhaps Refs. 26, 27, and 29).
