The timing of intermittent hypoxia differentially affects macronutrient intake and energy substrate utilization in mice.

Sleep apnea is a common sleep disorder characterized by periodic breathing cessation and intermittent hypoxia (IH). While previous studies have demonstrated that IH alone can influence metabolic outcomes such as body weight, it remains unclear how the timing of IH can specifically affect these outcomes. Here, we examine how pairing 10-hour periods of IH to either the animals' resting phase (e.g. IH during the day) or active phase (e.g. IH during the night) differentially affects body weight, macronutrient selection, energy expenditure, respiratory exchange rate, and glucose tolerance. We find that in contrast to mice exposed to IH during the night, mice exposed to IH during the day preferentially decrease their carbohydrate intake and switch to fat metabolism. Moreover when the IH stimulus was removed, mice that had been exposed to day IH continued to eat a minimal amount of carbohydrates and consumed a higher percentage of Kcal from fat for at least 5 days. These data demonstrate that food choice and substrate utilization are secondary to the timing of IH but not IH itself. Taken together, these data have key clinical implications for individuals with sleep apnea and particularly those who are also experiencing circadian disruption such as night-shift workers.

Anorexia and fat aversion induced by vertical sleeve gastrectomy is attenuated in neurotensin receptor 1 deficient mice

Neurotensin (NT) is an anorexic gut hormone and neuropeptide that increases in circulation following bariatric surgery in humans and rodents. We sought to determine the contribution of NT to the metabolic efficacy of vertical sleeve gastrectomy (VSG). To explore a potential mechanistic role of NT in VSG, we performed sham or VSG surgeries in diet-induced obese neurotensin receptor 1 (NTSR1) wildtype (wt) and knockout (ko) mice and compared their weight and fat mass loss, glucose tolerance, food intake, and food preference after surgery. NTSR1 ko mice had reduced initial anorexia and body fat loss. Additionally, NTSR1 ko mice had an attenuated reduction in fat preference following VSG. Results from this study suggest that NTSR1 signaling contributes to the potent effect of VSG to initially reduce food intake following VSG surgeries and potentially also on the effects on macronutrient selection induced by VSG. However, maintenance of long-term weight loss after VSG requires signals in addition to NT.

Balancing macronutrient intake in a mammalian carnivore: disentangling the influences of flavour and nutrition

There is a large body of research demonstrating that macronutrient balancing is a primary driver of foraging in herbivores and omnivores, and more recently, it has been shown to occur in carnivores. However, the extent to which macronutrient selection in carnivores may be influenced by organoleptic properties (e.g. flavour/aroma) remains unknown. Here, we explore the roles of nutritional and hedonic factors in food choice and macronutrient balancing in a mammalian carnivore, the domestic cat. Using the geometric framework, we determined the amounts and ratio of protein and fat intake in cats allowed to select from combinations of three foods that varied in protein : fat (P : F) composition (approx. 10 : 90, 40 : 60 and 70 : 30 on a per cent energy basis) to which flavours of different ‘attractiveness’ (fish, rabbit and orange) were added. In two studies, in which animal and plant protein sources were used, respectively, the ratio and amounts of protein and fat intake were very consistent across all groups regardless of flavour combination, indicating regulation of both protein and fat intake. Our results suggest that macronutrient balancing rather than hedonistic rewards based on organoleptic properties of food is a primary driver of longer-term food selection and intake in domestic cats.