Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

/pdf/metabolic-acceleration-and-the-evolution-of-human-brain-size-5bpo2q0jr3.pdf

Metabolic acceleration and the evolution of human brain size and life history

For decades, dietary advice was based on the premise that high intakes of fat cause obesity, diabetes, heart disease, and possibly cancer. Recently, evidence for the adverse metabolic effects of processed carbohydrate has led to a resurgence in interest in lower-carbohydrate and ketogenic diets with high fat content. However, some argue that the relative quantity of dietary fat and carbohydrate has little relevance to health and that focus should instead be placed on which particular fat or carbohydrate sources are consumed. This review, by nutrition scientists with widely varying perspectives, summarizes existing evidence to identify areas of broad consensus amid ongoing controversy regarding macronutrients and chronic disease.

Dietary fat: From foe to friend?

Microbiota Depletion Impairs Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue

The main focus of the International Journal of Obesity (IJO) is to better understand human obesity. Many scientists use rodents as convenient models to dissect aspects of physiology and body-weight control that would not be feasible in humans, such as invasive and terminal investigations. At present there is a range of commercial high-fat diets available that have been demonstrated to make small rodents obese. However, some of these diets contain levels of dietary fat that are much higher than the levels that humans routinely consume. The question has been raised as to whether experimental use of these diets with very high levels of fat adequately models the situation of human obesity. If not, the question arises whether the IJO should continue to accept such papers for publication. The Editorial Board of IJO was asked its views on this issue: 14 Board members replied (listed at the end). This short editorial summarises those responses. Several of the responses came from clinical scientists with no direct experience of performing work on rodents. Together they all reinforced the view that if rodent models can be made more closely to mimic what happens in humans then it is likely that the insights following from such work will be enhanced. There was also a strong feeling, however, that while the journal might advise what they think is best, they should not impose a ban on future papers for these methodological reasons. Many of the basic scientists with experience of using rodent models emphasised the reason and history behind the choice of diets containing 60% fat to create obesity in mice. At the moment the biggest supplier of rodent diets is the company Research Diets. About 20 years ago they created a series of 3 diets known as the DIO series. These had, respectively 10%, 45% and 60% fat by calories. A normal rodent diet contains about 10% fat, so both 45 and 60% fat diets are high-fat for rodents. Mice on the 45% fat diet become obese. However, mice on the 60% fat diet become more obese, and do so more rapidly. This is advantageous because it reduces the time that the animals need to be housed, thereby reducing caging costs. Many researchers therefore use the 60% rodent diet as a matter of economics and convenience. Some commercial suppliers of prefattened mice also use this diet to accelerate the fattening process and reduce the costs. The typical American or European diet, however, contains about 36–40% fat by energy, so a tolerable high-fat human diet might contain 50–60% of energy as fat. However, the 60% fat rodent diet presents a much greater distortion of the fat content of a normal rodent chow. Thus rodent studies with a 60% fat content are potentially not as relevant to human physiology as those which use a 45% fat diet. A key question then is whether there is any difference in the resultant obesity, physiology and metabolism of the mice fed high (c. 45%) vs. very high (c. 60%) fat diets. Several of the responses from the board addressed this issue directly and the answer seems to be that very high fat diets produce a more exaggerated metabolic response than highfat diets, but the difference is relatively small. For example, the extent of obesity and impacts on glucose homoeostasis and insulin resistance increase with increasing fat content up to around 60% fat [1, 2]. Although some studies have failed to detect such differences [3, 4]. Impacts on cognition with age appear relatively minor [4, 5]. A comparison of metabolite profiles of low-fat (10%) vs. high-fat diet (45% fat) vs. very high-fat diet (60% fat) fed mice revealed that 80 metabolites were altered in the lungs of high-fat fed mice relative to the control diet [6]. However, only 35 of these 80 changed metabolites were common across the two high-fat diets, indicating these diets generated rather different metabolic responses. This is not an exhaustive review but it * John R. Speakman j.speakman@abdn.ac.uk

/pdf/use-of-high-fat-diets-to-study-rodent-obesity-as-a-model-of-3pa6w28v1h.pdf

Use of high-fat diets to study rodent obesity as a model of human obesity

The carbohydrate-insulin model: a physiological perspective on the obesity pandemic.

Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice.

The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda–unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.

/pdf/exceptionally-low-daily-energy-expenditure-in-the-bamboo-d9jxsnynmi.pdf

Exceptionally low daily energy expenditure in the bamboo-eating giant panda

Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice

Objectives The carbohydrate-insulin model (CIM) predicts that increases in fasting and post-prandial insulin in response to dietary carbohydrates stimulate energy intake and lower energy expenditures, leading to positive energy balance and weight gain. The objective of the present study was to directly test the CIM's predictions using C57BL/6 mice. Methods Diets were designed by altering dietary carbohydrates with either fixed protein or fat content and were fed to C57BL/6 mice acutely or chronically for 12 weeks. The body weight, body composition, food intake, and energy expenditures of the mice were measured. Their fasting and post-prandial glucose and insulin levels were also measured. RNA-seq was performed on RNA from the hypothalamus and subcutaneous white adipose tissue. Pathway analysis was conducted using IPA. Results Only the post-prandial insulin and fasting glucose levels followed the CIM's predictions. The lipolysis and leptin signaling pathways in the sWAT were inhibited in relation to the elevated fasting insulin, supporting the CIM's predicted impact of high insulin. However, because higher fasting insulin was unrelated to carbohydrate intake, the overall pattern did not support the model. Moreover, the hypothalamic hunger pathways were inhibited in relation to the increased fasting insulin, and the energy intake was not increased. The browning pathway in the sWAT was inhibited at higher insulin levels, but the daily energy expenditure was not altered. Conclusions Two of the predictions were partially supported (and hence also partially not supported) and the other three predictions were not supported. We conclude that the CIM does not explain the impact of dietary macronutrients on adiposity in mice.

Lu Wang

Papers

Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice.

Exceptionally low daily energy expenditure in the bamboo-eating giant panda

Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice

The carbohydrate-insulin model does not explain the impact of varying dietary macronutrients on the body weight and adiposity of mice.