Experimental Antibiotic May Boost Metabolism and Mitigate Obesity

No clinical trial has been conducted to prove this concept in humans just yet, current fluoroquinolones are not to be used for weight control at this point.

WeightControl.com Interview with:
Dr. Marcelo Alves da Silva Mori PhD
Professor,University of Campinas 

WeightControl.com: What is the background for this study? What are the main findings?

Response: microRNAs are small non-coding RNAs that play important roles in gene expression regulation. Aging and obesity leads to dysfunction of microRNA processing in adipose tissue, which in turn impairs the thermogenic capacity of brown fat and results in insulin resistance. Enoxacin is a small molecule fluoroquinolone that promotes microRNA biogenesis.

In our most recent paper, we used enoxacin as proof of principle to demonstrate in mice and human cells that drugs targeting the microRNA processing pathway can be used to enhance oxidative metabolism and promote thermogenesis, thus mitigating obesity.  

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Older Patients Are Able to Lose Weight As Well as Younger Patients

Weight gain and obesity can affect anyone, regardless of age. There may be barriers that exist for older people with obesity.

Weightcontrol.com Interview with:
Dr. Thomas M Barber MRCP, PhD
Associate Professor
Honorary Consultant Endocrinologist
University of Warwick and UHCW NHS Trust

Dr. Barber

Weightcontrol.com: What is the background for this study? What are the main findings?

Response: Obesity management within the UK is structured into a 4-tiered system. Tier 3 refers to hospital-based management that usually consists of medical input combined with focused dietary and psychological support where required. Typically within hospital-based tier 3 obesity services, certain subgroups of the population are under-represented, including men and older people. There are likely multiple reasons for this. However, obesity can affect anyone regardless of sex, age or any other classification.

To improve the health and wellbeing of the nation, it is important that we facilitate effective weight management for as many people with obesity as possible. Much of the chronic effects of weight gain and obesity are similar to those that occur with ageing (including, for example increased cardiovascular risk). Therefore, older people with obesity can experience a type of ‘accelerated ageing’ with increased risk for co-morbidities and premature mortality.

The effective management of obesity is therefore particularly important for older people. Unfortunately, we live in an ageist society, which perhaps explains, at least in part, why older people are currently under-represented in obesity services provided by the NHS. The aim of our study was to explore the effects of older age on ability to lose weight within the context of a hospital-based tier 3 obesity service.

Efficacy and Safety of Setmelanotide For Patients with a Rare form of Genetic Obesity

The severe hyperphagia and the feeling of permanent failure due to the situation of being unable to reduce body weight with conservative treatment options (increase exercise, reduce caloric intake) may affect the relationship within the family

WeightControl.com Interview with:
Prof. Dr. Peter Kühnen
Institute for Experimental Pediatric Endocrinology
Charité Universitätsmedizin Berlin
Berlin, Germany

Prof. Dr. Peter Kühnen

WeightControl.com:  What is the background for this study?  What are the main findings?

Response: The leptin melanocortin signaling pathway plays a pivotal role for central appetite regulation. Gene mutations in this pathway are leading to severe hyperphagia and early onset obesity. We present the data of two phase 3 trials, in which patients with POMC/PCSK1 or LEPR deficiency received treatment with the MC4R agonist setmelanotide. In the past, there were centrally acting obesity drugs, like the cannabinoid receptor inhibitor rimonabant, whose use was associated with depression. Therefore, here we present the data about suicidality and depression of the participants during the treatment with the MC4R agonist setmelanotide.

The main finding was that there was no consistent increase in depression or suicidal ideation / behavior of the treated patients. However, in all cases depressive episode or increase in suicidal ideation was related to the medical history of the participants.

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Can a Ketogenic Diet Reverse Heart Failure?

It should be tested whether high fat or ketogenic diets can improve heart failure from typical etiologies such as myocardial infarction and chronic hypertension

WeightControl.com Interview with:
Kyle S. McCommis, Ph.D.
Assistant Professor
Biochemistry & Molecular Biology
St. Louis University School of Medicine

WeightControl.com:  What is the background for this study?  What are the main findings?

Response: It is well established that the heart is normally very flexible in what substrates it can metabolize in order to quickly adapt to different physiological scenarios. However, in cardiomyopathies such as heart failure, this metabolic flexibility is lost and there is a decreased ability for the heart to perform oxidative metabolism. This has previously been attributed mainly to a decrease in fat oxidation by the heart, but some studies also indicate decreased glucose oxidation.

We therefore were interested to see if the mitochondrial pyruvate carrier (MPC), which transports pyruvate derived from glucose or lactate into the mitochondria, could be playing a role in heart failure.

We first identified lower expression of the MPC proteins in failing human hearts compared to non-failing control hearts. We then created a MPC2 knockout mouse, which spontaneously developed heart failure with age. These failing hearts of course could not metabolize pyruvate, but they also displayed lower expression of fat oxidation enzymes.

We hypothesized that the hearts may be improved if we provided the mice with a diet that provided nutrients the hearts were better able to use. When we switched the diet to a low carbohydrate, high fat “ketogenic” diet, these MPC2 knockout mice no longer showed any signs of heart failure. We also aged some mice to where they developed severe heart failure, then switched them to the ketogenic diet, and shockingly observed almost complete reversal of their cardiac dysfunction. This lead us to question how the diet was rescuing these hearts; was it due to improved ketone body metabolism by the hearts, or due to improved fat metabolism from the large amount of dietary fat.

Essentially all of our experiments suggested that these failing hearts we regaining the ability to oxidize fatty acids, and were actually shutting off ketone body metabolism. Feeding the mice a normal “high fat” diet which contains enough carbohydrate and protein to not be overly ketogenic, was also able to prevent the heart failure in these mice.

Weight Loss in Low Income Patients in Primary Care Settings

Clinically significant weight loss is possible in underserved, low-income patients in primary care settings.

WeightControl.com Interview with:
Peter Katzmarzyk, Ph.D., FACSM, FAHA, FTOS
Professor and Marie Edana Corcoran Endowed Chair
Pediatric Obesity and Diabetes
Assoc Exec Dir for Population and Public Health Sciences
Pennington Biomedical Research Center
Baton Rouge, LA

WeightControl.com:  What is the background for this study?

Response: Obesity remains one of the greatest public health threats, and there is good evidence that intensive lifestyle interventions should be a primary approach to obesity management and treatment. However, there has been minimal uptake of obesity treatment approaches in primary care, which is the cornerstone of medicine in the US.

WeightControl.com: What are the main findings?

Response: We developed an intervention to reduce calorie intake and increase physical activity that was delivered by health coaches embedded in primary care clinics. The sample was diverse with a large percentage of low-income and African American patients. The results demonstrated that patients in the intensive lifestyle intervention lost approximately 5% of their initial body weight, compared to patients in usual care who lost about 0.5% of their body weight. These weight loss differences between the two groups were maintained out to 2 years, which demonstrates the durability of the intervention.    

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COVID-19 Linked to Difficulty with Weight Control

With the current concerns that the pandemic may lead to increases in obesity rates, it’s important to develop appropriate and large-scale support options for those aiming to manage their weight.

WeightControl.com Interview with:

Dr Sarah-Elizabeth Bennett
Senior Research Associate
Slimming World, UK

WeightControl.com:  What is the background for this study?

Response: This research is part of a larger Health and Wellbeing study, investigating the behaviour changes made by members of Slimming World, the UK’s largest group-based weight management organisation. New members were surveyed regularly over the course of one year and a representative sample of non-members were also surveyed at similar timepoints for comparison. The survey at the six-month point coincided with lockdown, so questions were added to learn more about how lockdown measures had impacted the nation’s health, wellbeing, and lifestyle behaviours. The following findings were based on the responses of 222 members who had completed all 3 surveys to-date and 637 non-members.

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Benefits of Weight Loss on Physical Function in Older Adults Differ by Sex and Race

We report greater weight loss-associated improvement in short physical performance battery score in women (versus men) and greater gait speed improvement in blacks (versus whites).

WeightControl.com Interview with:
Kristen M. Beavers, PhD, MPH, RD
Associate Professor
Department of Health and Exercise Science
Wake Forest University

WeightControl.com:  What is the background for this study?  What are the main findings?

Response: Consideration of differential treatment effects among subgroups in clinical trial research is a topic of increasing interest. This is an especially salient issue for weight loss trials, as most are over-represented by white women. The question we sought to address is: “Does sex or race moderate the effect of a weight loss intervention on physical function among older adults?”

In this pooled analysis of 1317 individuals participating in eight randomized clinical trials of weight loss — of which 30% were male and 21% were black — we report greater weight loss-associated improvement in short physical performance battery score in women (versus men) and greater gait speed improvement in blacks (versus whites).

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How Much Fasting Is Necessary to Lose Weight?

The main findings of this study were a 3% weight loss in 8 weeks in both groups with a 550-calorie restriction (unintentional) and good adherence to both diets.

MedicalResearch.com Interview with:
Sofia Cienfuegos
PhD Candidate, Human Nutrition.
Department of Kinesiology and Nutrition
University of Illinois at Chicago

MedicalResearch.com:  What is the background for this study?

Response: Intermittent fasting has been gaining a lot of popularity lately mainly due to a large group of the general population that don’t like to keep tabs on their caloric intake. Intermittent fasting is a safe and effective alternative to weight loss that does not require people consciously restricting calories. Time restricted feeding (TRF) is one specific type of IF that has been gaining a lot of popularity and public interest lately. Previous studies in TRF with the 16/8 method made people want to try and follow this diet strategy achieving promising results. Some people were wondering if shortening the feeding  window even further would induce better results in terms of weight loss and cardiometabolic health.

Based on this question, we decided to test two different short time restricted feeding methods (18/6 and 20/4) to see if they could induce even better results in weight and health outcomes. We were also wondering if people were able to stick to these interventions considering the short eating window.

MedicalResearch.com: What are the main findings?

Response: The main findings of this study were a 3% weight loss in 8 weeks in both groups with a 550-calorie restriction (unintentional) and good adherence to both diets. Also, we found significant reductions in insulin resistance and oxidative stress in both intervention groups.

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Scientists Explain Why Artificial Sweeteners Don’t Quench Our Appetite for Sugar

We identified a key gut-to-brain circuit responsible for our unquenchable sugar appetite.

WeightControl.com Interview with:
Alexander Sisti, MD/PhD Candidate
Zuker Lab
Columbia University

suga

WeightControl.com:  What is the background for this study? 

Response: Our lab has studied the biology of mammalian taste for over two decades. Previous work has identified the receptors for all five basic taste qualities (sweet, sour, bitter, salty, umami).

In the course of these studies, we generated mice lacking sweet receptors (i.e. “sweet-blind”). Unexpectedly, we observed that these animals could eventually learn to identify and develop a preference for a sugar-containing bottle—even though they could not taste it. This was not true for artificial sweeteners. This led us to hypothesize that there was something about the sugar that made the animals feel good and want more of it.

We set out to identify the brain circuits underlying our insatiable appetite for sugar which could operate independently from the taste system. So, we searched the brain for areas activated by sugar but not artificial sweeteners and areas that responded to sugar in the sweet-blind animals. We wanted to identify where the sugar signal was coming from.

WeightControl.com:  What are the main findings?

Response: Our work revealed that sugar activates a selective circuit from the gut to the brain. This pathway is responsible for our “wanting” of sugar. It does not respond to artificial sweeteners and operates completely independently from the classical tongue-to-brain taste system (which mediates “liking” of all sweet substances, including artificial sweeteners). The discovery of this new circuit fundamentally changes the way we think about the action of sugar in the brain.

WeightControl.com: What should readers take away from your report?

Response: Our most significant findings are:

  1. We identified a key gut-to-brain circuit responsible for our unquenchable sugar appetite.
  2. We demonstrate that silencing this circuit is able to completely abolish development of sugar preference. Essentially, we were able to create “sugar-blind” animals insensitive to sugar craving. Given the extraordinary impact of sugar on the global epidemic of obesity, metabolic syndrome and diabetes, identifying new strategies to curb sugar consumption could have a meaningful impact on human health.
  3. Our results explain why artificial sweeteners have failed in reducing our appetite for sugar, as they cannot activate this gut-brain circuit.

Citation:

Hwei-Ee Tan, Alexander C. Sisti, Hao Jin, Martin Vignovich, Miguel Villavicencio, Katherine S. Tsang, Yossef Goffer, Charles S. Zuker. The gut–brain axis mediates sugar preferenceNature, 2020; DOI: 10.1038/s41586-020-2199-7

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Weight Control: Better to Eat a Big Breakfast than Big Dinner

The importance of the time of day and our internal clock for food intake and energy metabolism is a very exciting research field. Future studies should investigate why we spend so much more energy after breakfast than after dinner

WeightControl.com Interview with:
M. Sc. Juliane Richter
University of Lübeck
Center of Brain, Behavior and Metabolism
Section of Psychoneurobiology

WeightControl.com:  What is the background for this study?  What are the main findings?

Response: The background for this study is that there is still the misbelief that it does not matter when we eat and that the only thing that counts is the energy balance of the whole day. However, since our body has an internal clock and many processes in the body, for example glucose metabolism, are subject to diurnal variations, we investigated whether diet-induced thermogenesis also varies during the course of the day.

Diet-induced thermogenesis is the energy our body spends for the digestion, absorption and transport of nutrients. We found that diet-induced thermogenesis after breakfast is more than twice as high as after dinner. We also investigated whether this difference in time of day depends on the amount of calories consumed. In both cases, high- and low-calorie meals, the body spends more energy after breakfast than after dinner.

breakfast-timing of meals for weight control
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